Search tips
Search criteria 


Logo of autophLink to Publisher's site
Autophagy. 2011 November; 7(11): 1273–1294.
Published online 2011 November 1. doi:  10.4161/auto.7.11.17661
PMCID: PMC3359482

A comprehensive glossary of autophagy-related molecules and processes (2nd edition)


The study of autophagy is rapidly expanding, and our knowledge of the molecular mechanism and its connections to a wide range of physiological processes has increased substantially in the past decade. The vocabulary associated with autophagy has grown concomitantly. In fact, it is difficult for readers—even those who work in the field—to keep up with the ever-expanding terminology associated with the various autophagy-related processes. Accordingly, we have developed a comprehensive glossary of autophagy-related terms that is meant to provide a quick reference for researchers who need a brief reminder of the regulatory effects of transcription factors and chemical agents that induce or inhibit autophagy, the function of the autophagy-related proteins, and the roles of accessory components and structures that are associated with autophagy.

Keywords: autophagy, lysosome, mitophagy, pexophagy, stress, vacuole


One meaning for the term “comprehensive” is to “cover completely or broadly.” However, the rapid expansion in the field of autophagy is such that this glossary will be out of date as soon as it is published. On the other hand, “comprehensive” can also indicate, “marked by or showing extensive understanding.” If we consider that our knowledge of autophagy has indeed expanded tremendously over the past decade, it may be appropriate to suggest that we are developing an extensive understanding of this subject. Of course we fully expect that our current understanding will undergo substantial change in the coming months and years, and that even the breadth of our knowledge may amount to little more than the tip of the autophagy iceberg. Nonetheless, we think it will be helpful to researchers to catalog the information we have about autophagy in an easily accessible format.

Accordingly, we present here the 2nd edition of a comprehensive glossary for autophagy, which is expanded by more than 62%. The definitions are purposely short; our intent is that the reader can gain a quick, rather than in-depth, understanding of the function or meaning of the relevant word. In addition, the references generally cite the first use of particular terms, or the first cloning of a gene and description of the corresponding protein, or an appropriate review article; due to space considerations, this list is far from being inclusive. We encourage readers to examine the primary literature for additional details about the process of autophagy and the components described herein.

3-MA (3-methyladenine): An inhibitor of class I and class III PtdIns 3-kinase, which results in autophagy inhibition due to suppression of class III PtdIns 3-kinase,1 but may under some conditions show the opposite effect.2

11′-deoxyverticillin A (C42): An epipolythiodioxopiperazine fungal secondary metabolite that is used as an anticancer drug; it triggers apoptotic and necrotic cell death, and enhances macroautophagy through the action of PARP-1 and RIP-1.3

12-ylation: The modification of substrates by covalent conjugation to Atg12, first used to describe the autocatalytic conjugation of Atg12 to Atg3.4

14-3-3ζ: A member of the 14-3-3 family of proteins that inhibits macroautophagy; direct interaction with hVps34 negatively regulates kinase activity, and this interaction is disrupted by starvation or C2-ceramide.5

A20: An E3 ubiquitin ligase that also functions as a deubiquitinating enzyme that removes K63-linked ubiquitin from Beclin 1, thus limiting macroautophagy induction in response to Toll-like receptor signaling.6

ABT737: A BH3 mimetic that competitively disrupts the interaction between Beclin 1 and Bcl-2 or Bcl-XL, thus inducing macroautophagy.7

Acinus: A protein that in Drosophila regulates both endocytosis and macroautophagy; the acn mutant is defective in autophagosome maturation, whereas overexpression of Acn leads to excessive macroautophagy.8

AEG-1 (astrocyte-elevated gene-1): This gene encodes an oncogenic protein that induces noncanonical (Beclin 1- and class III PtdIns 3-kinase-independent) macroautophagy as a cytoprotective mechanism.9

AEN/ISG20L1 (apoptosis-enhancing nuclease/interferon stimulated exonuclease gene 20 kDa-like 1): A protein that localizes to nucleolar and perinucleolar regions of the nucleus, which regulates macroautophagy associated with genotoxic stress; transcription of ISG20L1 is regulated by p53 family members.10

aggrephagy: The selective removal of aggregates by macroautophagy.11

AGS3 (activator of G protein signaling 3): A guanine nucleotide dissociation inhibitor for Gαi3 that promotes macroautophagy by keeping Gαi3 in an inactive state.12 AGS3 directly binds LC3 and recruits Gαi3 to phagophores or autophagosomes under starvation conditions to promote autophagosome biogenesis and/or maturation. See also Gαi3.

AICAR: Cell permeable nucleotide analogue, aminoimidazole-4-carboxamide riboside that is an activator of AMP kinase; inhibits autophagy14 through mechanisms that are not related to its effect on AMPK.14,16

AIM (Atg8-family Interacting Motif):17 See WXXL and LIR/LRS.

Alfy (autophagy-linked FYVE protein): An adaptor that targets cytosolic protein aggregates for autophagic degradation.18 Alfy interacts directly with Atg5 19 and with p62.20

ALR (autophagic lysosome reformation): A self-regulating process in which the macroautophagic generation of nutrients reactivates mTOR, suppresses macroautophagy and allows for the regeneration of lysosomes that were consumed as autolysosomes.21

Ambra1 (activating molecule in Beclin 1-regulated autophagy): A positive regulator of macroautophagy. Ambra1 binds Beclin 1 and modulates its activity.22

Amphisome: Intermediate compartment formed by the fusion of an autophagosome with an endosome (this compartment can be considered a type of autophagic vacuole and may be equivalent to a late autophagosome, and as such has a single limiting membrane); this compartment has not yet fused with a lysosome.23

AMPK (AMP-activated protein kinase): A sensor of energy level that is activated by an increase in the AMP/ATP ratio via the LKB1 kinase. Phosphorylates the mTORC1 subunit Raptor to cause induction of macroautophagy. AMPK also activates the TSC1/2 complex (thus inhibiting Rheb), and binds and directly phosphorylates (and activates) ULK1 as part of the ULK1 kinase complex, which includes mATG13 and FIP200.24,25 The yeast homolog of AMPK is Snf1.26,27 Conversely, ULK1 can phosphorylate AMPK through a negative feedback loop.27

APMA (autophagic macrophage activation): A collection of autophagy-related processes in cells of the reticulo-endothelial system. APMA includes (1) convergence of phagocytosis and the autophagic machinery, (2) enhanced microbicidal properties of autolysosomes in comparison to standard phagolysosomes, (3) autophagic modulation of pathogen recognition receptor (PRR) signaling, (4) cooperation between immunity-related GTPases and autophagy or Atg proteins in attacking parasitophorus vacuoles and (5) enhanced antigen presentation. APMA is thus recognized as a complex outcome of autophagy stimulation in macrophages, representing a unique composite process that brings about a heightened state of immunological activation.28

ARD1 (arrest-defective protein 1): A protein that interacts with and stabilizes TSC2 by acetylation, resulting in repression of mTOR and induction of macroautophagy.29

Atg (autophagy related): Abbreviation used for most of the components of the protein machinery that are involved in selective and nonselective macroautophagy and in selective microautophagy.30

Atg1: A serine/threonine protein kinase that functions in recruitment and release of other Atg proteins from the PAS.31 The functional homologs in higher eukaryotes are ULK1 and ULK2.

Atg2: A protein that acts along with Atg18 to mediate the retrograde movement of Atg9 away from the PAS.32,33

Atg3: A ubiquitin-conjugating enzyme (E2) analog that conjugates Atg8/LC3 to phosphatidylethanolamine (PE) after activation of the C-terminal residue by Atg7.34,35 ATG3 can also be conjugated to ATG12 in higher eukaryotes.4 See also 12-ylation.

Atg4: A cysteine protease that processes Atg8/LC3 by removing the amino acid residue(s) that are located on the C-terminal side of what will become the ultimate glycine. Atg4 also removes PE from Atg8/LC3 in a step referred to as “deconjugation.”36 Mammals have four Atg4 proteins (Atg4A-D), but Atg4B appears to be the most relevant for macroautophagy and has the broadest range of activity for all of the Atg8 homologs.37,38

Atg5: A protein containing ubiquitin folds that is part of the Atg12-Atg5-Atg16 complex, which acts in part as an E3 ligase for Atg8/LC3-PE conjugation.39

Atg6 (Vps30): A component of the class III PtdIns 3-kinase complex. Atg6 forms part of two distinct complexes (I and II) that are required for the Atg and Vps pathways, respectively. See also Beclin 1.40

Atg7: A ubiquitin-activating (E1) enzyme homolog that activates both Atg8/LC3 and Atg12 in an ATP-dependent process.41,42

Atg8: A ubiquitin-like protein that is conjugated to PE; involved in cargo recruitment into, and biogenesis of, autophagosomes. Autophagosomal size is regulated by the amount of Atg8. Since Atg8 is selectively enclosed into autophagosomes, its breakdown allows measurement of the autophagic rate. Mammals have several Atg8 homologs comprising the LC3 and GABARAP subfamilies, which are also involved in autophagosome formation.4345

Atg9: A transmembrane protein that may act as a lipid carrier for expansion of the phagophore. In mammalian cells, mAtg9A localizes to the trans-Golgi network and endosomes, whereas in fungi this protein localizes in part to reservoirs (termed the tubulovesicular cluster) that are localized near the mitochondria, and to the PAS.46,47 While mammalian mAtg9A is ubiquitously expressed, mAtg9B is almost exclusively expressed in the placenta and pituitary gland.48

Atg10: A ubiquitin-conjugating (E2) enzyme analog that conjugates Atg12 to Atg5.49

Atg11: A fungal scaffold protein that acts in selective types of macroautophagy including the Cvt pathway, mitophagy and pexophagy. Atg11 binds Atg19, PpAtg30 and Atg32 as part of its role in specific cargo recognition. It also binds Atg9 and is needed for its movement to the PAS.50

Atg12: A ubiquitin-like protein that modifies an internal lysine of Atg5 by covalently binding via its C-terminal glycine.39 In mouse and human cells, ATG12 also forms a covalent bond with ATG3, and this conjugation event plays a role in mitochondrial homeostasis.4 See also 12-ylation.

Atg13: A component of the Atg1 complex that is needed for Atg1 kinase activity. Atg13 is highly phosphorylated in a PKA- and Tor-dependent manner in rich medium conditions. During starvation-induced macroautophagy in yeast, Atg13 is partially dephosphorylated. In mammalian cells, at least Tor and Ulk1/Atg1 phsophorylate Atg13. The decreased phosphorylation of Atg13 that results from Tor inhibition is partly offset by the Ulk1-dependent phosphorylation that occurs upon Ulk1 activation.51,52

Atg14: A component of the class III PtdIns 3-kinase complex that is necessary for the complex to function in macroautophagy.40

Atg15: A vacuolar protein that contains a lipase/esterase active site motif and is needed for the breakdown of autophagic and Cvt bodies within the vacuole lumen.53,54

Atg16: A component of the Atg12-Atg5-Atg16 complex. Atg16 dimerizes to form a large complex.55 There are two mammalian homologs, Atg16L1 and Atg16L2. The former is one of the risk alleles associated with Crohn disease.56

Atg17: A yeast protein that is part of the Atg1 kinase complex. Atg17 is not essential for macroautophagy, but modulates the magnitude of the response; smaller autophagosomes are formed in the absence of Atg17.57,58

Atg18: A protein that binds to PtdIns(3)P (and PtdIns(3,5) P2 via its WD40 β-propeller domain. Atg18 functions along with Atg2 in the retrograde movement of Atg9. Atg18 has additional nonautophagic functions, such as in retrograde transport from the vacuole to the Golgi complex, and in the regulation of PtdIns(3,5)P2 synthesis; the latter function affects the vacuole's role in osmoregulation.59 See also WIPI.

Atg19: A receptor for the Cvt pathway that binds Atg11, Atg8 and the propeptide of precursor aminopeptidase I. Atg19 is also a receptor for α-mannosidase, another Cvt pathway cargo.60,61

Atg20: A PtdIns(3)P binding protein that is part of the Atg1 kinase complex.62

Atg21: A PtdIns(3)P binding protein that is a homolog of, and partially redundant with, Atg18.63 See also WIPI.

Atg22: A vacuolar amino acid permease that is required for efflux after autophagic breakdown of proteins.64,65

Atg23: A yeast protein that transits with Atg9.6668

Atg24 (Snx4): A PtdIns(3)P binding protein that is part of the Atg1 kinase complex.62

Atg25: A coiled-coil protein required for macropexophagy in Hansenula polymorpha.69

Atg26: A sterol glucosyltransferase that is required for micro- and macropexophagy in Pichia pastoris, but not in Saccharomyces cerevisiae.70,71

Atg27: An integral membrane protein that is required for the movement of Atg9 to the PAS. The absence of Atg27 results in a reduced number of autophagosomes under autophagy-inducing conditions.72

Atg28: A coiled-coil protein involved in micro- and macropexophagy in P. pastoris.73

Atg29: A protein required for efficient nonspecific macroautophagy in fungi. Part of an Atg17-Atg31-Atg29 complex that functions at the PAS for protein recruitment.74

Atg30: A protein required for the recognition of peroxisomes during micro- and macropexophagy in P. pastoris. It binds the peroxin PpPex14 and the selective autophagy adaptor protein PpAtg11.75

Atg31: A protein required for nonspecific macroautophagy in fungi. Part of an Atg17-Atg31-Atg29 complex that functions at the PAS for protein recruitment.76

Atg32: A mitochondrial outer membrane protein that is required for mitophagy in fungi. Atg32 binds Atg8 and Atg11 preferentially during mitophagy-inducing conditions.77,78

Atg33: A mitochondrial outer membrane protein that is required for mitophagy in fungi.79

Atg34: A protein that functions as a receptor for import of α-mannosidase during macroautophagy (i.e., under starvation conditions) in yeast.80 This protein was initially referred to as Atg19-B based on predictions from in silico studies.81 See also Atg19.

Atg35: The Atg35 protein relocates to the perinuclear structure (PNS) and specifically regulates MIPA formation during micropexophagy in P. Pastoris; the atg35Δ mutant is able to form pexophagosomes during macropexophagy.82

Atg101: An Atg13-binding protein conserved in various eukaryotes but not in S. cerevisiae. Forms a stable complex with ULK1/2-Atg13-FIP200 (i.e., not nutrient-dependent), required for macroautophagy and localizes to the phagophore.83,84

ATM (ataxia-telangiectasia mutated): A protein kinase that activates TSC2 via the LKB1-AMPK cascade in response to elevated ROS, resulting in inhibition of mTOR and activation of macroautophagy.85

autolysosome: A degradative compartment formed by the fusion of an autophagosome (or initial autophagic vacuole/AVi) or amphisome with a lysosome (also called degradative autophagic vacuole/AVd or autophagolysosome). Upon completion of degradation this compartment again becomes a lysosome or residual body.22,86

autophagic body: The inner membrane-bound structure of the autophagosome that is released into the vacuolar lumen following fusion of the autophagosome with the vacuole limiting membrane. In S. cerevisiae, autophagic bodies can be stabilized by the addition of the proteinase B inhibitor PMSF to the medium. Visualization of the accumulating autophagic bodies by Nomarski optics is a convenient method to follow macroautophagy.87

autophagic cell death: A historically ambiguous term describing cell death with morphological features of increased autophagic vacuoles. This term is best reserved for cell death contexts in which specific molecular methods, rather than only pharmacological or correlative methods, are used to demonstrate increased cell survival following inhibition of autophagy.

autophagic stress: A pathological situation in which induction of autophagy exceeds the cellular capacity to complete lysosomal degradation and recycling of constituents; may involve a combination of bioenergetics, acidification and microtubule-dependent trafficking deficits, to which neurons may be particularly vulnerable.88

autophagist: A researcher working in the field of autophagy.

autophagosome: A cytosolic membrane-bound compartment denoted by a limiting double membrane (also referred to as initial autophagic vacuole, AVi or early autophagosome). The early autophagosome contains cytoplasmic inclusions and organelles that are morphologically unchanged because the compartment has not fused with a lysosome and lacks proteolytic enzymes. Although in most cases the term autophagosome refers to a double-membrane vesicle, the late autophagosome may also appear to have a single membrane (also referred to as an intermediate autophagic vacuole, AVi/d).22,86

autophagy: This term summarizes all processes in which intracellular material is degraded within the lysosome/vacuole and where the macromolecular constituents are recycled.

Autophagy: A journal devoted to research in the field of autophagy ( Also, a forum ( where you can obtain practical information from active researchers regarding the usefulness of commercially available reagents, such as antibodies to specific autophagy-related proteins.

bafilomycin A1 (BA/BAF): An inhibitor of the vacuolar (V)-type ATPase that alters the pH and membrane potential of acidic compartments, which ultimately results in a block in fusion of autophagosomes with lysosomes, thus preventing the maturation of autophagosomes into autolysosomes.89,90 Note that the abbreviation for bafilomycin A1 is not “BFA,” as the latter is the standard abbreviation for brefeldin A.

BAG3 (Bcl-2-associated athanogene 3): A stress-induced co-chaperone that interacts with dynein; BAG3 directs Hsp70 misfolded protein substrates to dynein, which targets them to aggresomes, leading to their selective degradation by macroautophagy via a ubiquitin-independent mechanism.91

Barkor (Beclin 1-associated autophagy related key regulator): Also known as Atg14L, the mammalian homolog of yeast Atg14, a component of the class III PtdIns 3-kinase complex.92

basal autophagy: Constitutive autophagic degradation that proceeds in the absence of any overt stress or stimulus. Basal autophagy is important for the clearance of damaged proteins and organelles in normal cells (especially fully differentiated, nondividing cells), and becomes elevated in response to stress; for example, in certain tumor cells, basal autophagy increases in response to strong oncogenic insults.93,94

BATS (barkor/Atg14(L) autophagosome targeting sequence) domain: A protein domain within Atg14L that is required for the recruitment of the PtdInsKC3 to LC3-containing puncta during macroautophagy induction; the predicted structure of the BATS domain suggests that it senses membrane curvature.95

Bck1: A MAPKKK downstream of Pkc1 and upstream of Mkk1/2 and Slt2 that controls cell integrity in response to cell wall stress; Bck1 is required for pexophagy96 and mitophagy.97 See also Slt2 and Hog1.

Bcl-2 family of proteins: There are two general classes of Bcl-2 proteins; anti-apoptotic proteins include Bcl-2, Bcl-XL, Bcl-w and Mcl-1 that inhibit macroautophagy, and pro-apoptotic BH3-only proteins include BNIP3, Bad, Bik, Noxa, Puma and BimEL that induce macroautophagy. Interaction of Bcl-2 with Beclin 1 prevents the association of the latter with the class III PtdIns 3-kinase.

Beclin 1 (Bcl-2 interacting myosin/moesin-like coiled-coil protein 1): A mammalian homolog of yeast Atg6/Vps30 that forms part of the class III PtdIns 3-kinase complex involved in activating macroautophagy.98

BH3 domain: A Bcl-2 homology (BH) domain that is found in all Bcl-2 family proteins, whether they are pro-apoptotic or anti-apoptotic. A BH3 domain is also present in Beclin 1 and mediates the interaction with anti-apoptotic proteins possessing a BH3 receptor domain (i.e., Bcl-2, Bcl-XL, Bcl-w and Mcl-1).

BH3-only proteins: A series of proteins that contain a BH3 domain (but not any other Bcl-2 homology, BH, domains). Several BH3-only proteins (BNIP3, Bad, Bik, Noxa, Puma and BimEL) can competitively disrupt the inhibitory interaction between Bcl-2 and Beclin 1 to allow the latter to act as an allosteric activator of PtdIns 3-kinase and to activate macroautophagy.

Bif-1 (Bax-interacting factor 1)/endophilin B1: A protein that interacts with Beclin 1 via UVRAG and is required for macroautophagy. Bif-1 has a BAR domain that may be involved in deforming the membrane as part of autophagosome biogenesis.99

BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3): A member of the BH3-only subfamily of Bcl-2 family proteins. Originally classified as a pro-apoptotic protein, it is required for the HIF-1-dependent induction of macroautophagy during hypoxia by disrupting the interaction of Beclin 1 with Bcl-2.100,101

CAL-101: A small molecule inhibitor of the p110d subunit of class 1A PtdIns 3-kinase; treatment of multiple myeloma cells results in macroautophagy induction.102

calpains: A class of calcium-dependent, nonlysosomal cysteine proteases that cleave and inactivate ATG5 and the ATG12-ATG5 conjugate, hence establishing a link between reduced Ca2+ concentrations and induction of autophagy.103

CaMKKβ (calcium/calmodulin-dependent protein kinase kinase-β): Activates AMPK in response to an increase in the cytosolic calcium concentration,104 resulting in the induction of macroautophagy.105

CAPNS1 (calpain small 1): The regulatory subunit of micro- and millicalpain; CAPSN1-deficient cells are autophagy defective and display a substantial increase in apoptotic cell death.106

CASA (chaperone-assisted selective autophagy): A degradative process that utilizes the Drosophila co-chaperone Starvin or its mammalian homolog BAG3 to direct the degradation of aggregated substrates through the action of Hsc70, HspB8, the CHIP ubiquitin ligase and p62.107 The requirement for ubiquitination of, and the absence of a requirement for the KFERQ motif in, the substrates, along with the involvement of the ATG proteins differentiate this process from CMA, which also uses chaperones for lysosome-dependent degradation.

caspases (cysteine-dependent aspartate-directed proteases): A class of proteases that play essential roles in apoptosis (programmed cell death type I) and inflammation. Several pro-apoptotic caspases cleave essential autophagy proteins, resulting in the inhibition of autophagy.108

CCI-779 (temsirolimus): A water-soluble rapamycin ester that induces macroautophagy.

Cdc48: A protein that extracts ubiquitinated proteins from the membrane as part of ERAD, but is also required for nonspecific macroautophagy in yeast.109 See also Shp1 and VCP.

CD46: A cell-surface glycoprotein that interacts with the scaffold protein GOPC to mediate an immune response to invasive pathogens including Neisseria and Group A Streptococcus. Interaction of pathogens via the Cyt1 cytosolic tail induces autophagy, which involves GOPC binding to Beclin 1. CD46 is also used as a cellular receptor by several pathogens.110

chaperone-mediated autophagy (CMA): An autophagic process in mammalian cells by which proteins containing a particular pentapeptide motif related to KFERQ are transported across the lysosomal membrane and degraded.111,112 The translocation process requires the action of the integral membrane protein LAMP-2A and both cytosolic and lumenal hsc70.113,114

chloroquine (CQ): Chloroquine and its derivatives (such as 3-hydroxychloroquine) raise the lysosomal pH and ultimately inhibit the fusion between autophagosomes and lysosomes, thus preventing the maturation of autophagosomes into autolysosomes, and blocking a late step of macroautophagy.115

c-Jun: A mammalian transcription factor that inhibits starvation-induced macroautophagy.116

Clg1: A yeast cyclin-like protein that interacts with Pho85 to induce macroautophagy by inhibiting Sic1.117

COG (conserved oligomeric Golgi) Complex: A cytosolic tethering complex that functions in the fusion of vesicles within the Golgi complex, but also participates in macroautophagy and facilitates the delivery of Atg8 and Atg9 to the PAS.118

crinophagy: Selective degradation of secretory granules by autophagy.119 See also zymophagy.

cryptides: Peptides with a cryptic biological function that are released from cytoplasmic proteins by partial degradation or processing through macroautophagy (e.g., neoantimocrobial peptide released from ribosomal protein rps30).120

cysmethynil: A small-molecule inhibitor of isoprenylcysteine carboxylmethyl-transferase; treatment of PC3 cells causes an increase in LC3-II and cell death with macroautophagic features.121

cytoplasm-to-vacuole targeting (Cvt): A constitutive, biosynthetic pathway in yeast that transports resident hydrolases to the vacuole through a selective macroautophagy-like process.122

DAP1 (death-associated protein 1): A conserved phosphoprotein that is a substrate of mTOR and inhibits macroautophagy; inhibition of mTOR results in dephosphorylation of DAP1 and inhibition of macroautophagy, thus limiting the magnitude of the autophagic response.123

DAPK (death-associated protein kinase): A kinase that phosphorylates Thr119 of Beclin 1 to activate it by causing dissociation from Bcl-xL and Bcl-2, thus activating macroautophagy.124

Desat1: A Drosophila lipid desaturase that localizes to autophagosomes under starvation conditions; the Desat mutant is defective in macroautophagy induction.125

DFCP1 (double FYVE domain-containing Protein 1): A PtdIns(3)P-binding protein that localizes to the omegasome.126 Knockdown of DFCP1 does not result in an autophagy-defective phenotype.

diacylglycerol: A lipid second messenger that contributes to macroautophagic targeting of Salmonella-containing vacuoles.127

DJ-1/PARK7: An oncogene product whose loss-of-function is associated with Parkinson disease; overexpression suppresses macroautophagy through the JNK pathway.128

DOR (diabetes- and obesity-regulated gene/TP53INP2): A mammalian and Drosophila regulatory protein that shuttles between the nucleus and the cytosol; the cytosolic protein interacts with LC3 and GATE-16 and stimulates autophagosome formation.129 See also TP53INP2.

DRAM (damage-regulated autophagy modulator): A p53 target that encodes a lysosomal protein that induces macroautophagy.130

Draper: A Drosophila homolog of the Caenorhabditis elegans engulfment receptor CED-1 that is required for macroautophagy associated with cell death during salivary gland degradation, but not for starvation-induced macroautophagy in the fat body.131

Drs: An apoptosis-inducing tumor suppressor that is involved in the maturation of autophagosomes.132

E2F1: A mammalian transcription factor that upregulates the expression of LC3, ULK1 and DRAM directly, and ATG5 indirectly.133 E2F1 plays a role during DNA damage-induced macroautophagy.

eF1α (elongation factor 1α): Multifunctional member of the faimily of G-proteins with different cellular variants. The lysosomal variant of this protein acts coordinately with GFAP at the lysosomal membrane to modulate the stability of the CMA translocation complex. Release of membrane-bound eF1α in a GTP-dependent manner promotes disassembly of the translocation complex and consequently reduces CMA activity.134

eIF2α kinase (eukaryotic initiation factor 2α kinase): There are four mammalian eIF2α kinases that respond to different types of stress. PKR and PERK induce macroautophagy in response to virus infection and ER stress, respectively.135,136 See also Gcn2, PKR and PERK.

endosomal microautophagy (e-MI): A form of autophagy in which cytosolic proteins are sequestered into late endosomes/multivesicular bodies through a microautophagy-like process. Sequestration can be nonspecific or can occur in a selective manner mediated by hsc70. This process differs from chaperone-mediated autophagy as it does not require substrate unfolding and it is independent of the CMA receptor LAMP-2A.137 This process occurs during MVB formation and requires the ESCRT I and ESCRT III protein machinery. See also endosome and multivesicular body.

endosome: The endosomal compartment receives molecules engulfed from the extracellular space. It consists of several discrete subcompartments including the early endosome, and the recycling endosome (recycles material back to the plasma membrane). In mammalian cells, early and/or multivesicular endosomes fuse with autophagosomes to generate amphisomes.

epg (ectopic PGL granules) mutants: C. elegans mutants that are defective in the macroautophagic degradation of PGL-1, SEPA-1 and/or T12G3.1/p62.138 The EPG-3 and EPG-7 proteins are homologs of VMP1 and FIP200, respectively, whereas EPG-1 may be a homolog of Atg13.139

ERK1/2 (extracellular signal regulated protein kinase 1/2): A kinase that phosphorylates and stimulates Gα-interacting protein (GAIP), which is a GAP for the trimeric Gi3 protein that activates macroautophagy,140 and which may be involved in Beclin 1-independent autophagy.141 Constitutively active ERK1/2 also traffics to mitochondria to activate mitophagy.142

Everolimus (RAD-001): An mTOR inhibitor similar to rapamycin that induces macroautophagy.

Exo84: A component of the exocyst complex, and an effector of RalB that is involved in nucleation and/or expansion of the phagophore; Exo84 binds RalB under nutrient-poor conditions, and stimulates the formation of a complex that includes ULK1 and the class III PtdIns3K.143 See also RalB and Sec5.

Exophagy: A process used for protein secretion that is independent of the secretory pathway, and dependent on Atg proteins; acyl-coenzyme A-binding protein (Acb1) uses this route for delivery to the cell surface.144146

Fasudil: A Rho-associated kinase (ROCK) inhibitor that enhances macroautophagy.147

FIP200 [focal adhesion kinase (FAK) family interacting protein of 200 kDa/RB1CC1 (retinoblastoma 1 inducible coiled coil-1)]: A putative mammalian functional counterpart of yeast Atg17. FIP200 is a component of the ULK1 complex.148

FKBP12 (FK506-binding protein 12): An immunophilin that forms a complex with rapamycin and inhibits mTOR.

FKBP51 (FK506-binding protein 51): An immunophilin that forms a complex with FK506 and rapamycin; FKBP51 promotes autophagy in irradiated melanoma cells, thus enhancing resistance to radiation therapy.149

FNBP1L (formin binding protein 1-like): An F-BAR-containing protein that interacts with Atg3 and is required for the autophagy-dependent clearance of Salmonella Typhimurium, but not other types of autophagy.150

FoxO1 (forkhead box O1): A mammalian transcription factor that regulates macroautophagy independent of transcriptional control; the cytosolic form of FoxO1 is acetylated after dissociation from sirtuin-2 (SIRT2), and binds Atg7 to allow induction of macroautophagy in response to oxidative stress or starvation.151 FoxO1 can also be deacetylated by SIRT1, which leads to upregulation of Rab7 and increased autophagic flux.152 See also SIRT1.

FoxO3 (forkhead box O3): A transcription factor that stimulates macroautophagy through transcriptional control of autophagy-related genes.153,154

FYCO1 (FYVE and coiled-coil domain containing 1): A protein that interacts with LC3, PtdIns(3)P and Rab7 to move autophagosomes toward the lysosome through microtubule plus end-directed transport.155

Gαi3: A heterotrimeric G protein that activates macroautophagy in the GDP-bound (inactive) form, and inhibits it when bound to GTP (active state).156,157 See also AGS3 and GIV.

GABARAP (gamma-aminobutyric acid receptor-associated protein): A homolog of LC3.158,159 The GABARAP family includes GABARAP, GABARAPL1, GABARAPL2/GATE-16 and GABARAPL3. The GABARAP proteins are involved in autophagosome formation and cargo recruitment.45

Gadd34 (growth arrest and DNA damage protein 34): A protein that is upregulated by growth arrest and DNA damage; Gadd34 binds to and dephosphorylates TSC2, leading to mTOR suppression and autophagy induction.160

GAIP (Gα-interacting protein): A GTPase activating protein that inactivates Gαi3 (converting it to the GDP-bound form) and stimulates macroautophagy.161 See also Gαi3.

GATE-16 (Golgi-associated ATPase enhancer of 16 kDa/GABARAPL2): A homolog of LC3.158,159

Gcn2: A mammalian and yeast eIF2α serine/threonine kinase that phosphorylates and activates Gcn4 in response to amino acid depletion, which positively regulates macroautophagy.135

Gcn4: A transcriptional activator that controls the synthesis of amino acid biosynthetic genes and positively regulates macroautophagy in response to amino acid depletion.135

GFAP (glial fibrilary acid protein): Intermediate filament protein ubiquitiously distributed in all cell types that bears functions beyond filament formation. Monomeric and dimeric forms of this protein associate with the cytosolic side of the lysosomal membrane and contribute to modulating the stability of the CMA translocation complex in a GTP-dependent manner coordinated with eF1α also at the lysosomal membrane.134

Gfer (growth factor erv1-like): A flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase that is part of a disulfide redox system in the mitochondrial intermembrane space, and is also present in the cysosol and nucleus. Downregulation of Gfer results in elevated levels of the mitochondrial fission GTPase Drp1, and decreased mitophagy.162

GIV (Gα-interacting, vesicle-associated protein/Girdin): A guanine nucleotide exchange factor for Gαi3 that acts to downregulate macroautophagy.12 GIV disrupts the AGS3-Gαi3 complex in response to growth factors, releasing the G protein from the phagophore or autophagosome membrane; Gαi3-GTP also activates the class I PtdIns3K, thus inhibiting macroautophagy. See also Gαi3.

GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein/PIST/FIG/CAL): Interacts with Beclin 1, and the SNARE protein Syntaxin 6. GOPC can induce autophagy via a CD46-Cyt-1-dependent pathway following pathogen invasion.110

Gpnmb (glycoprotein nonmetastatic melanoma B/DC-HIL/osteoactivin): A protein involved in kidney repair that controls the degradation of phagosomes through macroautophagy.163

GSK-3β (glycogen synthase kinase-3β): A positive regulator of macroautophagy that inhibits mTOR by activating TSC1/2.

HDAC6 (histone deacetylase 6): A microtubule-associated deacetylase that interacts with ubiquitinated proteins. HDAC6 stimulates autophagosome-lysosome fusion by promoting the remodeling of F actin, promoting the quality control function of macroautophagy.164166

HIF-1 (hypoxia-inducible factor 1): A dimeric transcription factor in which the α subunit is regulated by oxygen; the hydroxylated protein is degraded by the proteasome. HIF-1-mediated expression of BNIP3 results in the disruption of the Bcl-2-Beclin 1 interaction, thus inducing macroautophagy.167,168

HMGB1 (high mobility group box 1): A chromatin-associated nuclear protein that translocates out of the nucleus in response to stress such as ROS; HMGB1 binds to Beclin 1, displacing Bcl-2, thus promoting macroautophagy and inhibiting apoptosis.169 In addition, macroautophagy promotes the release of HMGB1 from the nucleus and the cell, and extracellular HMGB1 can further induce macroautophagy through binding RAGE.170,171 See also RAGE.

Hog1: A MAPK involved in hyperosmotic stress, which is a homolog of mammalian p38; Hog1 is required for mitophagy, but not other types of selective autophagy or nonspecific autophagy.97 See also Pbs2, Slt2 and p38.

hsc70 (heast shock cognate of the Hsp70 family): This multifunctional cytosolic chaperone is the constitutive member of the hsp70 family of chaperones and participates in targeting of cytosolic proteins to lysosomes for their degradation via chaperone-mediated autophagy (CMA).172 The cytosolic form of the protein also regulates the dynamics of the CMA receptor, whereas the lumenal form (lys-hsc70) is required for substrate translocation across the membrane.173 Recently, this chaperone has been shown to play a role in the targeting of aggregated proteins (in a KFERQ-independent maner) for macroautophagy degradation through chaperone-assisted selective autophagy,107 and in KFERQ-dependent targeting of cytosolic proteins to late endosomes for microautophagy.137 See also chaperone-assisted selective autophagy, chaperone-mediated autophagy and endosomal microautophagy.

hsp90 (heat shock protein 90): Cytosolic chaperone also located in the lysosome lumen. The lysosomal form of hsp90 contributes to the stabilization of LAMP-2A during its lateral mobility in the lysosomal membrane.174

ICP34.5: A neurovirulence gene product encoded by the herpes simplex virus type 1 (HSV-1) that blocks eIF2α/PKR induction of autophagy.135 ICP34.5-dependent inhibition of autophagy depends upon its ability to bind to Beclin 1.175

IKK (IκB kinase): An activator of the classical NFκB pathway composed of three subunits (IKKα, IKKβ, IKKγ, the latter also called NEMO) that are required for optimal induction of macroautophagy in human and mouse cells.176

immunoamphisomes: An organelle derived from the fusion of endosomes/phagosomes with autophagosomes that regulate dendritic cell-mediated innate and adaptive immune responses.177

immunophagy: The sum of diverse immunological functions of autophagy.178

inositol monophosphatase: An enzyme that regulates the level of myo-inositol-1,4,5-triphosphate (IP3) levels. Inhibition of inositol monophosphatase stimulates autophagy independently of mTOR.179

IP3R (inositol-1,4,5-triphosphate receptor): A Ca2+ channel present in the endoplasmic reticulum that controls the steady-state Ca2+ level in the ER. IP3R is activated by IP3, regulated by Bcl-2-like proteins, and acts as an inhibitor of autophagy, forming a multiprotein complex that comprises Bcl-2 and Beclin 1.179

IRGM (p47 immunity-related GTPase): Involved in the macroautophagic control of intracellular pathogens.180

isolation membrane: See phagophore.

JNK1 (c-Jun N-terminal kinase 1): A stress-activated kinase that phosphorylates Bcl-2 at Thr69, Ser70 and Ser87, causing its dissociation from Beclin 1, thus inducing macroautophagy.181

Jumpy/MTMR14: A member of the myotubularin family that is a PtdIns 3-phosphatase; knockdown increases macroautophagic activity.182 Jumpy regulates the interaction of WIPI-1 with the phagophore.

JunB: A mammalian transcription factor that inhibits starvation-induced macroautophagy.116

Ku-0063794: A catalytic mTOR inhibitor that increases macroautophagic flux to a greater level than allosteric inhibitors such as rapamycin; short-term treatment with Ku-0063794 can inhibit both mTORC1 and mTORC2, but the effects on flux are due to the former.183 See also WYE-354.

Laforin: A member of the dual-specificity protein phosphatase family that acts as a positive regulator of macroautophagy probably by inhibiting mTOR, as laforin deficiency causes increased mTOR activity.184 Mutations in the genes encoding laforin or the putative E3-ubiquitin ligase malin, which form a complex, are associated with the majority of defects causing Lafora disease, a type of progressive neurodegeneration.

LAMP-2 (lysosome-associated membrane protein type 2): A widely expressed and abundant single-span lysosomal membrane protein.185 Three spliced variants of the lamp2 gene have been described. Knockout of the entire gene results in altered intracellular vesicular trafficking, defective lysosomal biogenesis, inefficient autophagosome clearance and alterations in intracellular cholesterol metabolism.186188

LAMP-2A (lysosome-associated membrane protein 2A): One of the spliced variants of the lamp2 gene that functions as a lysosomal membrane receptor for chaperone-mediated autophagy.114 LAMP-2A forms multimeric complexes that allow translocation of substrates across the lysosome membrane.174 Regulation of LAMP-2A is partly achieved by dynamic movement into and out of lipid microdomains in the lysosomal membrane.173

LC3 (microtubule-associated protein 1 light chain 3): A homolog of yeast Atg8, which is frequently used as a phagophore or autophagosome marker. Cytosolic LC3-I is conjugated to phsophatidylethanolamine to become phagophore- or autophagosome-associated LC3-II.189 The LC3 family includes LC3A, LC3B and LC3C. These proteins are involved in the biogenesis of autophagosomes, and in cargo recruitment.45 Vertebrate LC3 is regulated by phosphorylation of the N-terminal helical region by protein kinase A.190 See also GABARAP.

LC3-associated phagocytosis: Phagocytosis in macrophages that involves the conjugation of LC3 to single membrane phagosomes, a process that promotes phagosome acidification and fusion with lysosomes.191 TLR signaling is required for LC3-associated phagocytosis and leads to the recruitment of the Beclin 1 complex to phagosomes. See also NADPH oxidase.

lipophagy: Selective degradation of lipid droplets by lysosomes contributing to lipolysis (breakdown of triglycerides into free fatty acids). In mammals, this selective degradation has been described to occur via macroautophagy (macrolipophagy),192 whereas in yeast, microlipophagy of cellular lipid stores has also been described.

LIR/LRS (LC3-interacting region/LC3 recognition sequence): This term refers to the WXXL-like sequences found in Atg19, Atg32, NBR1, NIX and p62 that link these proteins to Atg8/LC3 (see also AIM and WXXL-motif).193

LKB1 (Serine/Threonine Kinase 1): A kinase that is upstream of, and activates, AMPK.194

LLPD (long-lived protein degradation): Macroautophagy is the primary mechanism used by cells to degrade long-lived proteins, and a corresponding assay can be used to monitor autophagic flux;195 a useful abbreviation for long-lived protein degradation is LLPD.196

lucanthone: An anti-schistome compound that inhibits a late stage of macroautophagy; treatment results in deacidification of lysosomes and the accumulation of autophagosomes.197

LRRK2 (leucine-rich repeat kinase 2): A large multidomain, membrane-associated kinase and GTPase whose Parkinson disease-associated mutations affect regulation of autophagy.198,199

LRSAM1 (leucine-rich repeat and sterile α-motif containing 1): A human leucine-rich repeat protein that potentially interacts with GABARAPL2; knockdown of LRSAM1 results in a defect in anti-Salmonella autophagy.200

LY294002: An inhibitor of PtdIns 3-kinases; it inhibits macroautophagy.201

lysosome: A degradative organelle in higher eukaryotes that compartmentalizes a range of hydrolytic enzymes and maintains a highly acidic pH.

macroautophagy: An autophagic process involving the formation of an autophagosome, a double- or multiple-membrane cytosolic vesicle of non-lysosomal/vacuolar origin.

MAP1LC3 (microtubule-associated protein 1 light chain 3): See LC3.

MDC (monodansylcadaverine): A lysosomotropic autofluorescent compound that accumulates in acidic compartments such as autolysosomes, and also labels (but is not specific for) autophagosomes.202,203

microautophagy: An autophagic process involving direct uptake of cytosol, inclusions (e.g., glycogen) and organelles (e.g., ribosomes, peroxisomes) at the lysosome/vacuole by protrusion, invagination or septation of the sequestering organelle membrane.

MIPA (micropexophagic apparatus): A curved double-membrane structure formed by the PAS that may serve as a scaffold for completion of the sequestration of peroxisomes during micropexophagy; fusion with the vacuolar sequestering membranes encloses the organelles within an intralumenal vesicle.204

mitophagy: The selective degradation of mitochondria; can occur by a micro- or macroautophagic process.205

Mkk1/2: A MAPKK downstream of Bck1 that is required for mitophagy and pexophagy.97 See also Bck1 and Slt2.

MTMR3 (myotubularin-related phosphatase 3): This protein localizes to the phagophore and negatively regulates macroautophagy (see Jumpy/MTMR14).206

mTOR (mammalian target of rapamycin): The mammalian ortholog of TOR. Together with its binding partners it forms either mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2). See also TORC1 and TORC2.

multivesicular body (MVB)/multivesicular endosome: An endosome containing multiple 50- to 80-nm vesicles that are derived from invagination of the limiting membrane. Under some conditions the MVB contains hydrolytic enzymes in which case it may be considered to be a lysosome or autolysosome with ongoing microautophagy.

multivesicular body (MVB) sorting pathway: A process in which proteins are sequestered into vesicles within the endosome through the invagination of the limiting membrane. This process is usually, but not always, dependent upon ubiquitin tags on the cargo and serves as one means of delivering integral membrane proteins destined for degradation into the vacuole/lysosome lumen. ESCRT (endosomal sorting complex required for transport) complexes are required for the formation of MVBs and for autophagosome maturation.

NADPH oxidases (NOX): These enzymes contribute to macroautophagic targeting of Salmonella in leukocytes and epithelial cells through the generation of reactive oxygen species.207 The NOX2 NADPH oxidase in macrophages is required for LC3-associated phagocytosis.

NAF-1 (nutrient-deprivation autophagy factor-1/CISD2): An integral membrane component that associates with the inositol-1,4,5-triphosphate receptor complex; NAF-1 binds Bcl-2 at the ER, and is required for Bcl-2 to bind Beclin 1, resulting in the inhibition of macroautophagy.208 CISD2 was reported to be associated with the ER, but the majority of the protein is localized to mitochondria, and mutations in CISD2 are associated with Wolfram syndrome 2; accelerated autophagy in Cisd2-/- mice may cause mitochondrial degradation, leading to neuron and muscle degeneration.209

NBR1 (neighbor of BRCA1 gene 1): A selective substrate of macroautophagy with structural similarity to p62. Functions as an adaptor that binds ubiquitinated proteins and LC3 to allow the degradation of the former by macroautophagy.193

NDP52 (nuclear dot protein 52 kDa): An adaptor that binds to the bacterial ubiquitin coat and Atg8/LC3 to target invasive bacteria, including Salmonella enterica serovar Typhimurium and Streptococcus pyogenes for autophagosomal sequestration.210

necroptosis: A form of programmed necrotic cell death;211 induction of macroautophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance.212

NFκB (nuclear factor kappa-light chain-enhancer of activated B cells): Activates mTOR to inhibit macroautophagy.213

NH4Cl (ammonium chloride): A weak base that is protonated in acidic compartments and neutralizes them; inhibits the clearance of autophagosomes and amphisomes.

NIX (NIP3-like X; BNIP3L/BNIP3α): A Bcl-2 related protein that is required for selective mitochondrial clearance (mitophagy) during erythroid differentiation.214

Nod (nucleotide-binding oligomerization domain): An intracellular peptidoglycan (or pattern recognition) receptor that senses bacteria and induces macroautophagy, involving ATG16L1 recruitment to the plasma membrane during bacterial cell invasion.215

noncanonical autophagy: A functional macroautophagy pathway that only uses a subset of the characterized Atg proteins to generate an autophagosome. At present, Beclin 1-independent,141,216 and Atg5-Atg7-independent217 forms of macroautophagy have been reported.

OATL1: A Tre2-Bub2-Cdc16 (TBC) domain-containing GTPase activating protein for Rab33B; OATL1 is recruited to phagophores and autophagosomes via direct interaction with the Atg8 family proteins (via a LIR/LRS-like sequence), and it regulates the interaction of autophagosomes with lysosomes by inactivating Rab33B.218 Overexpression of OATL1 inhibits autophagosome maturation at a step prior to fusion, suggesting that it might interfere with a tethering/docking function of Rab33B. See also Rab33B and LIR.

omegasome: DFCP1-containing structures located at the ER that are involved in autophagosome formation during amino acid starvation.126

Omi/HtrA2 (high temperature requirement factor A2): A serine protease that degrades Hax-1, a Bcl-2 family-related protein, to allow macroautophagy induction; knockdown of Omi, or the presence of a protease-defective mutant form, results in decreased basal macroautophagy and may lead to neurodegeneration.219

p8 (Nupr1): A transcriptional regulator that controls macroautophagy by repressing the transcriptional activity of FoxO3.220

p27 (p27Kip1): A cyclin-dependent kinase inhibitor that is phosphorylated and stabilized by an AMPK-dependent process and stimulates macroautophagy.194

p38α (mitogen-activated protein kinase isoform p38α): A signaling component that negatively regulates the interaction of mAtg9 and p38IP, and thus inhibits macroautophagy. The yeast homolog is Hog1. See also Hog1.

p38IP [p38α interacting protein/family with sequence similarity 48A (FAM48A)]: A protein that interacts with the C-terminal domain of mAtg9; this interaction is negatively regulated by p38α.221

p53: A tumor suppressor. Nuclear p53 activates autophagy, at least in part, by stimulating AMPK and DRAM. Cytoplasmic p53 inhibits autophagy.222

p62 (sequestosome 1/SQSTM1): A selective substrate of macroautophagy, that functions as an adaptor protein that links ubiquitinated proteins to LC3. p62 accumulates in cells when macroautophagy is inhibited. p62 interaction with LC3 requires a WXXL or a LIR motif analogous to the interaction of Atg8 with Atg19.223

p97: See VCP.

p110β: A catalytic subunit of the class IA PtdIns 3-kinase; this subunit plays a positive role in macroautophagy induction that is independent of mTOR or PKB/Akt, and instead acts through the generation of PtdIns(3)P, possibly by acting as a scaffold for the recruitment of phosphatases that act on PtdIns(3,4,5)P3 or by recruiting and activating Vps34.224

Parkin: An E3 ubiquitin ligase (mutated in autosomal recessive forms of Parkinson disease) that is recruited from the cytosol to mitochondria with a low membrane potential to promote their clearance by mitophagy.225

PARL (presenilin associated rhomboid-like): The mammalian homolog of Drosophila rhomboid-7, a mitochondrial protease; regulates the stability and localization of PINK1. A missense mutation in the N terminus has been identified in some patients with Parkinson disease.226

PARP-1 (poly [ADP-ribose] polymerase 1): A nuclear enzyme involved in DNA damage repair; doxorubicin-induced DNA damage elicits a macroautophagic response that is dependent on PARP-1.227 In conditions of oxidative stress, PARP-1 promotes macroautophagy through the LKB1-AMPK-mTOR pathway.228

PAS (phagophore assembly site): Also referred to as the preautophagosomal structure. A perivacuolar compartment or location that is the proposed nucleation site for sequestering vesicles (e.g., autophagosomes and Cvt vesicles) used in macroautophagylike processes in fungi. The PAS may supply membranes during the formation of the sequestering vesicles or may be an organizing center where most of the macroautophagic machinery resides at least transiently. The PAS or its equivalent is yet to be defined in mammalian cells.229,230

Pbs2: A MAPKK upstream of Hog1 that is required for mitophagy.97

Pcl1: A yeast cyclin that activates Pho85 to stimulate macroautophagy by inhibiting Sic1.117

Pcl5: A yeast cyclin that activates Pho85 to inhibit macroautophagy through degradation of Gcn4.117

PDK1 (phosphoinositide-dependent protein kinase 1): An activator of PKB/Akt. Recruited to the plasma membrane and activated by PtdIns(3,4,5)P3 which is generated by the class I PtdIns 3-kinase.

PEA-15/PED (phosphoprotein enriched in astrocytes 15 kDa/phosphoprotein enriched in diabetes): A death effector domain-containing protein that modulates JNK in glioma cells to promote macroautophagy.231

PERK (PKR-like ER kinase): A mammalian eIF2α kinase that may induce macroautophagy in response to ER stress.136

PES (2-phenylethynesulfonamide): A small molecule inhibitor of HSP70; PES interferes with lysosomal function, causing a defect in macroautophagy and chaperone-mediated autophagy.232

pexophagy: A selective type of autophagy involving the sequestration and degradation of peroxisomes; it can occur by a micro- or macroautophagic process (micro- or macropexophagy).233

phagophore: Membrane cisterna that is involved in an initial event during formation of the autophagosome. Also referred to as the “isolation membrane,” the phagophore is the initial sequestering compartment of macroautophagy.234

Pho80: A yeast cyclin that activates Pho85 to inhibit macroautophagy in response to high phosphate levels.117

Pho85: A multifunctional cyclin-dependent kinase that interacts with at least ten different cyclins or cyclin-like proteins to regulate the cell cycle and responses to nutrient levels. Pho85 acts to negatively and positively regulate macroautophagy, depending on its binding to specific cyclins.117 See also Clg1, Pcl1, Pcl5, Pho80 and Sic1.

phosphatidylinositol (PtdIns) 3-kinase (PtdIns3K): A family of enzymes that add a phosphate group to the 3′ hydroxyl on the inositol ring of phosphoinositides. The class III PtdIns 3-kinases (see Vps34; also referred to as PtdIns3KC3) are stimulatory for macroautophagy, whereas class I enzymes are inhibitory. So far, nothing is known about the involvement of the class II enzymes in autophagy.

piecemeal microautophagy of the nucleus (PMN)/micronucleophagy: A process in which portions of the yeast nuclear membrane and nucleoplasm are invaginated into the vacuole, scissioned off from the remaining nuclear envelope and degraded within the vacuole lumen.235,236

PINK1 (PTEN-induced kinase 1/PARK6): A mitochondrial protein (mutated in autosomal recessive forms of Parkinson disease) that is normally processed in a membrane potential-dependent manner to maintain mitochondrial function,237 suppressing the need for autophagy.238 Upon mitochondrial depolarization, this processing is arrested so that PINK1 spans the outer mitochondrial membrane, recruiting Parkin to facilitate mitophagy.239

PKA (protein kinase A): A serine/threonine kinase that negatively regulates macroautophagy in yeast,240 as well as in mammalian cells through direct phosphorylation of LC3.190 Bacterial toxins that activate PKA can also inhibit autophagy.241

PKB (protein kinase B) or Akt: A serine/threonine kinase that negatively regulates macroautophagy.

Pkc1: A protein serine/threonine kinase involved in the cell wall integrity pathway upstream of Bck1; required for pexophagy and mitophagy.97 See also Bck1 and Slt2.

PKCδ (protein kinase Cδ): PKCδ regulates JNK activation. PKCδ also activates NADPH oxidases, which are required for antibacterial macroautophagy.242

PKR (dsRNA-dependent protein kinase R): A mammalian eIF2α kinase that induces macroautophagy in response to viral infection.243

PGRP (peptidoglycan-recogntion protein): A cytosolic Drosophila protein that induces autophagy in response to invasive Listeria monocytogenes.244

PNS (peri-nuclear structure): A punctate structure in P. pastoris marked by Atg35, which requires Atg17 for recruitment and is involved in micropexophagy; the PNS may be identical to the PAS.245

presenilin: A protease that is part of the γ-secretase complex. Mutations in presenilin 1 result in the accumulation of autophagosomes resulting at least in part from a defect in lysosomal acidification; one of the V-ATPase subunits does not target properly to the lysosome.246,247

programmed cell death (PCD): Regulated self-destruction of a cell. Type I is associated with apoptosis and is marked by cytoskeletal breakdown and condensation of cytoplasm and chromatin followed by fragmentation. Type II is associated with macroautophagy and is characterized by the presence of autophagic vacuoles (autophagosomes) that sequester organelles. Type III is marked by the absence of nuclear condensation, and the presence of a necrotic morphology with swelling of cytoplasmic organelles (oncosis).

protolysosomes: Vesicles derived from autolysosomes that mature into lysosomes during autophagic lysosome reformation (see ALR).20

PTEN (phosphatase and tensin homolog): A 3′ phosphoinositide phosphatase that dephosphorylates PtdIns(3,4,5)P3, thereby inhibiting PDK1 and PKB/Akt activity.

PTPσ (protein tyrosine phosphatase sigma): A dual-domain protein tyrosine phosphatase that antagonizes the action of the class III PtdIns3K; loss of PTPσ results in hyperactivation of basal and induced macroautophagy.248

Rab1: See Ypt1.

Rab7: A small GTP binding protein functioning in transport from early to late endosomes and from late endosomes to lysosomes.249 Rab7 is also needed for the clearance of autophagic compartments, most likely for the fusion of amphisomes with lysosomes.250,251 The yeast homolog is Ypt7.

Rab24: A small GTP binding protein with unusual characteristics that associates with autophagic compartments in amino acid-starved cells.252

Rab32: A small GTP binding protein that localizes to the endoplasmic reticulum, and enhances autophagosome formation under basal conditions.253

Rab33B: A Rab protein of the medial Golgi complex that binds Atg16L1 and plays a role in autophagosome maturation by regulating fusion with lysosomes.254 Rab33B is a target of OATL1, which functions as a GAP.255

RabG3b: A Rab GTPase that functions in the differentiation of tracheary elements of the Arabidopsis xylem through its role in macroautophagy; this protein is a homolog of Rab7/Ypt7.256

RAD001 (Everolimus): An orally administered derivative of rapamycin.

Rag (Ras-related GTPase): A GTPase that activates TORC1 in response to amino acids.257

RAGE (peceptor for advanced glycation end products): A member of the immunoglobulin gene superfamily that binds the high mobility group box 1 chromatin binding protein (HMGB1); RAGE overexpression enhances macroautophagy and reduces apoptosis.258 This can occur in response to ROS, resulting in the upregulation of macroautophagy and the concomitant downregulation of apoptosis, favoring tumor cell survival in response to anticancer treatments that increase ROS production.259 See also HMGB1.

RalB: A GTPase that regulates exocytosis and the immune response; in nutrient-rich conditions RalB-GTP binds Sec5, whereas under starvation conditions, RalB-GTP nucleates phagophore formation through assembly of a ULK1-Beclin 1-VPS34 complex via interaction with the Exo84 protein.143 RalB may be an analog of yeast Sec4.260 See also Exo84, Sec4 and Sec5.

rapamycin: TOR (TOR complex 1) inhibitor, which induces autophagy. TOR complex 2 is much less sensitive to inhibition by rapamycin.

Rb-E2F1 (retinoblastoma protein-E2 transcription factor 1): Rb is a tumor suppressor that promotes growth arrest, and protects against apoptosis. E2F1 regulates the transition from the G1 to the S phase in the cell cycle, and is a pro-apoptotic member of the E2F transcription family. In addition to controlling the cell cycle and apoptosis, the interaction between Rb and E2F1 regulates macroautophagy; RB and E2F1 downregulate and upregulate Bcl-2, respectively, resulting in the induction of macroautophagy or apoptosis.261

reactive oxygen species (ROS): These are chemically-reactive molecules that contain oxygen, including hydrogen peroxide, the hydroxyl radical OH, and the superoxide radical O2. Hydrogen peroxide transiently inhibits delipidation of LC3 by Atg4, which is permissive for starvation-induced autophagy.262 Superoxide is essential for triggering injury-induced mitochondrial fission and mitophagy.238

residual body: A lysosome that contains indigestible material such as lipofuscin.263

resveratrol: An allosteric activator of Sirtuin 1 that induces macroautophagy.264

reticulophagy: The selective degradation of endoplasmic reticulum by a macroautophagy-like process.265

Rheb (Ras homolog enriched in brain): A small GTP-binding protein that activates TOR when it is in the GTP-bound form.266

Ribophagy: The selective degradation of ribosomes by macroautophagy.267

Rim15: A yeast kinase that regulates transcription factors in response to nutrients. Rim15 positively regulates macroautophagy and is negatively regulated by several upstream kinases including Tor, PKA, Sch9 and Pho85.117,268

RNS2: A class II RNase of the T2 family that localizes to the lumen of the endoplasmic reticulum (or an ER-related structure) and vacuole in Arabidopsis; RNS2 is involved in rRNA turnover, and rns2 mutants display constitutive macroautophagy, likely due to a defect in cellular homeostasis.269

rubicon (RUN domain protein as Beclin 1-interacting and cysteine-rich CONtaining): Rubicon is part of a PtdIns 3-kinase complex (Rubicon-UVRAG-Beclin 1-hVps34-p150) that localizes to the late endosome/lysosome and inhibits macroautophagy.270,271

Sch9: A kinase that functions in parallel with PKA to negatively regulate macroautophagy. Sch9 appears to function in parallel with TOR, but is also downstream of the TOR kinase.268

SEA (Seh1-associated) protein complex: A complex found in yeast that includes the Seh1 nucleoporin and the COPII component Sec13 (also a nucleoporin), in addition to Npr2 and Npr3, and four other relatively uncharacterized proteins; the SEA complex associates with the vacuole, potentially acting as a membrane coat and is involved in protein trafficking, amino acid biogenesis, and the starvation response including macroautophagy.272

Sec1: Functions with the plasma membrane SNAREs Sso1/Sso2 and Sec9 to form the site for vesicle-mediated exocytosis; as with Sso1/Sso2 and Sec9, temperature sensitive sec1 mutations also abrogate autophagic delivery of GFP-Atg8.273 See also Sso1/Sso2.

Sec2: A guanine nucleotide exchange factor for Sec4 that normally functions in exocytosis. Upon the induction of macroautophagy, Sec2 function is diverted to promote membrane delivery to the PAS.260

Sec4: A Rab family GTPase that normally functions in exocytosis; under macroautophagy-inducing conditions Sec4 is needed for the anterograde movement of Atg9 to the PAS.260

Sec5: A component of the exocyst complex; Sec5 binds RalB, Beclin 1, mTORC1, ULK1 and VPS34 under nutrient-rich conditions and prevents these components from interacting with Exo84, thus inhibiting macroautophagy.143 See also RalB and Exo84.

Sec9: Plasma membrane SNARE light chain that forms a complex with Sso1/Sso2 to generate the target complex of vesicle exocytosis; as with Sso1/Sso2, loss of Sec9 function blocks autophagy at an early stage by disrupting targeting of Atg9 to the tubulovesicular cluster and PAS.273 See also Sso1/Sso2.

Sec18: Homolog of the mammalian NSF, an ATPase globally responsible for SNARE disassembly. Loss of function inhibits SNARE-dependent early and late events of macroautophagy (i.e., vesicular delivery of Atg9 to the tubulovesicular cluster and PAS,273 and fusion of autophagosomes with the vacuole274).

Sec22: A vesicle SNARE involved in ER and Golgi transport; mutations in Sec22 also block Atg9 trafficking to the tubulovesicular cluster and PAS. Crosslinking experiments suggest Sec22 may be the v-SNARE responsible for the autophagy functions of the ordinarily plasma membrane Sso1/Sso2-Sec9 t-SNARE complex.273 See also Sso1/Sso2.273

SEPA-1 (suppressor of ectopic P granule in autophagy mutants-1): A C. elegans protein that is involved in the selective degradation of P granules through macroautophagy.275

septin cages: Septins are GTP-binding proteins that assemble into nonpolar filaments (characterized as unconventional cytoskeleton), often acting as scaffolds for the recruitment of other proteins. Septin cages form in response to infection by Shigella; the cages surround the bacteria, preventing intercellular spread, and serve to recruit autophagy components such as p62 and LC3.276

Sestrin 2: A protein encoded by a p53 target-induced gene that inhibits mTORC1 and induces macroautophagy, also acting as an AMPK activator.

Shp1/Ubx1: A Ubx (ubiquitin regulatory x)-domain protein that is needed for the formation of autophagosomes during nonselective macroautophagy; Shp1 binds Cdc48 and Atg8-PE, and may be involved in extracting the latter during phagophore expansion.109

Sic1: A yeast cyclin-dependent kinase inhibitor that blocks the activity of Cdc28-Clb kinase complexes to control entry into the S phase of the cell cycle. Sic1 is a negative regulator of macroautophagy that inhibits Rim15.117

sirolimus: An immunosuppressant also referred to as rapamycin.

SIRT1 (Sirtuin 1): A NAD+-dependent protein deacetylase that is activated by caloric restriction or glucose deprivation; SIRT1 can induce macroautophagy through the deacetylation of autophagy-related proteins and/or FoxO transcription factors.277

SLAPs (spacious listeria-containing phagosomes): SLAPs can be formed by Listeria monocytogenes during infection of macrophages or fibroblasts if bacteria are not able to escape into the cytosol.278 SLAPs are thought to be immature autophagosomes in that they bear LC3 but are not acidic and do not contain lysosomal degradative enzymes. The pore-forming toxin listeriolysin O is essential for SLAPs formation and is thought to create small pores in the SLAP membrane that prevent acidification by the v-ATPase. SLAP-like structures have been observed in a model of chronic L. monocytogenes infection,279 suggesting that autophagy may contribute to the establishment/maintenance of chronic infection.

SLC1A5 (solute carrier family 1 member 5): A high affinity, Na+-dependent transporter for L-glutamine; a block of transport activity leads to inhibition of mTORC1 signaling and the subsequent activation of autophagy.280 See also SLC7A5.

SLC7A5 (solute carrier family 7 member 5/SLC3A2): A bidirectional transporter that allows the simultaneous efflux of L-glutamine and influx of L-leucine; this transporter works in conjunction with SLC1A5 to regulate mTORC1.280

Slg1 (Wsc1): A cell surface sensor in the Slt2 MAPK pathway that is required for mitophagy.97 See also Slt2.

SLR (sequestosome 1/p62-like receptor): Receptors that act as autophagic adaptors, and in proinflammatory or other types of signaling.281

Slt2: A MAPK that is required for pexophagy and mitophagy.97 See also Pkc1, Bck1 and Mkk1/2.

smARF (short mitochondrial ARF): A small isoform of p19ARF that results from the use of an alternate translation initiation site, which localizes to mitochondria and disrupts the membrane potential, leading to a massive increase in macroautophagy and cell death.282

Snapin: An adaptor protein involved in dynein-mediated late endocytic transport; snapin is needed for the delivery of endosomes from distal processes to lysosomes in the neuronal stroma, allowing maturation of autolysosomes.283

spermidine: A natural polyamine that induces macroautophagy through the inhibition of histone acetylases.284

sphingolipids: Sphingolipids are a major class of lipids. Some metabolites including ceramide, sphingosine and sphingosine 1-phosphate are bioactive signaling molecules. Ceramide and sphingosine 1-phosphate are positive regulators of macroautophagy.285,286

Spinster: A putative lysosomal efflux permease required for autophagic lysosome reformation.287

Sqa (spaghetti-squash activator): A myosin light chain kinase-like protein that is a substrate of Atg1 in Drosophila; required for starvation-induced autophagosome formation, and the mammalian homolog ZIPK (zipper-interacting protein kinase) is also involved in mAtg9 trafficking.288

Ssk1: A component of the Hog1 signaling cascade that is required for mitophagy.97 See also Hog1.

Sso1/Sso2: Highly homologous plasma membrane syntaxins (SNAREs) of S. cerevisiae involved in exocytosis; the Sso1/Sso2 proteins also control the movement of Atg9 to the tubulovesicular cluster and PAS during macroautophagy and the Cvt pathway.273

Syntaxin-5: A Golgi-localized SNARE protein involved in vesicular transport of lysosomal hydrolases, a process that is critical for lysosome biogenesis; syntaxin-5 is needed for the later stages of autophagy.289

TAK1 (transforming growth factor-β-activating kinase 1): Required for TRAIL-induced activation of AMPK. Required for optimal macroautophagy induction by multiple stimuli.290

TAKA (transport of Atg9 after knocking out ATG1) assay: An epistasis analysis that examines the localization of Atg9-GFP in a double mutant, where one of the mutations is a deletion of ATG1.58 In atg1Δ mutants, Atg9-GFP is restricted to the PAS; if the second mutation results in a multiple puncta phenotype, the corresponding protein is presumably required for anterograde transport of Atg9 to the PAS.291 This analysis can be combined with localization of RFP-Ape1 to determine if any of the Atg9-GFP puncta reach the PAS, in which case that punctum would colocalize with the RFP-Ape1 PAS marker.

TASCC (TOR-autophagy spatial coupling compartment): A compartment located at the trans-Golgi where autolysosomes and mTOR accumulate during Ras-induced senescence to provide spatial coupling of protein secretion (anabolism) with degradation (catabolism); for example, amino acids generated from autophagy would quickly reactivate mTOR, whereas autophagy would be rapidly induced via mTOR inhibition when nutrients are again depleted.292

Tecpr1 (tectonin domain-containing protein): A protein that interacts with Atg5 and WIPI-2, and localizes to the phagophore (localization is dependent on WIPI-2); Tecpr1 is needed for phagophore formation during macroautophagic elimination of Shigella, but not for starvation-induced autophagy.293 Tecpr1 also localizes to autophagosomes that target other pathogenic microbes such as group A Streptococcus, to depolarized mitochondria and to protein aggregates, suggesting a general role in selective macroautophagy.

TFEB (transcription factor EB): A transcription factor that positively regulates the expression of genes involved in lysosomal biogenesis (those in the Coordinated Lysosomal Expression and Regulation network), and also several of those involved in macroautophagy (including UVRAG, WIPI, MAP1LC3B and ATG9B); the use of a common transcription factor allows the coordinated expression of genes whose products are involved in the turnover of cytoplasm.294

TGFβ (transforming growth factor-β): A cytokine that activates autophagy through the Smad and JNK pathways. TGFβ induces the expression of several ATG genes including BECN1.

TIGAR (TP53-induced glycolysis and apoptosis regulator): A protein that modulates glycolysis, causing an increase in NADPH, which results in a lower ROS level; this reduces the sensitivity to oxidative stress and apoptosis, but also has the effect of lowering the level of macroautophagy.295

Tlg2: Endocytic SNARE light chain involved in early stages of the Cvt pathway296 and in autophagosome membrane formation.273 Deletion of TLG2 results in a modest impairment in Atg9 delivery to the PAS.

TLR (toll-like receptor): A family of receptors that induces autophagy following binding to a corresponding pathogen-associated molecular pattern (PAMP).

TM9SF1: A protein with nine transmembrane domains that induces autophagy when overexpressed.297

TMEM: TMEM74 and TMEM166 are integral membrane proteins that induce autophagy when overexpressed.298,299

TOR (target of rapamycin): A protein kinase that negatively regulates macroautophagy. Present in two complexes, TORC1 and TORC2. TORC1 is particularly sensitive to inhibition by rapamycin. TORC1 regulates macroautophagy in part through Tap42-PP2A, and also by phosphorylating Atg13 and Atg1.

TORC1 (TOR complex 1): A rapamycin-sensitive protein complex of TOR that includes Tor1/Tor2 (mTOR), Kog1 (Raptor), Lst8 (mLST8), Rhb1 (Rheb) and Tco89.300 mTORC1 also includes DEPTOR.301 In mammalian cells, sensitivity to rapamycin is conferred by Raptor. TORC1 directly regulates macroautophagy.

TORC2 (TOR complex 2): A relatively rapamycin-insensitive protein complex of TOR that includes Tor2 (mTOR), Avo1 (SIN1), Avo2, Avo3 (Rictor), Bit2, Bit61, Lst8 (mLST8) and Tsc11; mTORC2 also includes DEPTOR, FKBP38, PRAS40 and Protor-1.300302 The main difference relative to TORC1 is the replacement of Raptor by Rictor. TORC2 is primarily involved with regulation of the cytoskeleton.

Torin1: A selective ATP-competitive mTOR inhibitor that directly inhibits both TORC1 and TORC2.303

TP53INP1 (tumor protein 53-induced nuclear protein 1): A stress-response protein that promotes p53 activity; cells lacking TP53INP1 display reduced basal and stress-induced autophagy.304

TP53INP2 (tumor protein 53-induced nuclear protein 2): Interacts with VMP1 and is needed for the recruitment of Beclin 1 and LC3 to autophagosomes. Translocates from the nucleus to autophagosomes during autophagy induction and binds VMP1 and LC3 directly.305 See also DOR.

TRAF6 (tumor necrosis factor receptor-associated factor 6): An E3 ubiquitin ligase that ubiquitinates Beclin 1 to induce TLR4-triggered macroautophagy in macrophages.6

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand): Induces autophagy by activating AMPK, thus inhibiting mTORC1 during lumen formation.

TRAPPIII (transport protein particle III): A guanine nucleotide exchange factor for Ypt1 that functions in macroautophagy in yeast.306 TRAPPIII is composed of Bet3, Bet5, Trs20, Trs23, Trs31, Trs33 and a unique subunit, Trs85.

TRS85: A component of the TRAPPIII complex that is required specifically for macroautophagy.

TSC1/2 (tuberous sclerosis complex 1/2): A stable heterodimer (composed of hamartin and tuberin) inhibited by PKB/Akt and ERK1/2 (phosphorylation causes dissociation of the dimer), and activated by AMPK. TSC1/2 acts as a GAP for Rheb, thus inhibiting TOR.

ubiquilins (UBQLNs): Adaptor proteins that deliver ubiquitinated substrates to the proteasome. Ubiquilins may aid in the incorporation of protein aggregates into autophagosomes, and also promote the maturation of autophagosomes at the stage of fusion with lysosomes.307

ubiquitin: A 76-kDa protein that is conjugated to lysine residues. Ubiquitin is traditionally considered part of the ubiquitinproteasome system and tags proteins for degradation; however, ubiquitin is also linked to various types of autophagy including aggrephagy (see p62 and NBR1).

ULK family (Unc51-like kinase): Homolog of yeast Atg1. In mammalian cells consists of five members, ULK1, ULK2, ULK3, ULK4, STK36/fused (ULK5). ULK1 and ULK2 are required for macroautophagy and ULK3 for oncogene-induced senescence.308310

UVRAG (UV irradiation resistance-associated gene): A Vps38 homolog that can be part of the class III PtdIns 3-kinase complex. UVRAG functions in several ways to regulate macroautophagy: (1) It disrupts Beclin 1 dimer formation and forms a heterodimer that activates macroautophagy; (2) it binds to Bif-1 to allow activation of class III PtdIns 3-kinase to stimulate macroautophagy; (3) it interacts with the class C Vps/HOPS proteins involved in fusion of autophagosomes or amphisomes with the lysosome; (4) it competes with Atg14L for binding to Beclin 1, thus directing the class III PtdIns 3-kinase to function in the maturation step of macroautophagy.311

vacuole: The yeast equivalent of the lysosome; this organelle also carries out storage and osmoregulatory functions.

vacuole import and degradation (Vid): A degradative pathway in yeast in which a specific protein(s) is sequestered into small single-membrane cytosolic vesicles that fuse with the vacuole allowing the contents to be degraded in the lumen. This process has been characterized for the catabolite-induced degradation of the gluconeogenic enzyme fructose-1,6-bisphosphatase in the presence of glucose, and sequestration is thought to involve translocation into the completed vesicle. An alternate pathway for degradation of fructose-1,6-bisphosphatase by the ubiquitinproteasome system has also been described.312

Vam3: A syntaxin homolog needed for the fusion of autophagosomes with the vacuole.313

VAMP3: A SNARE protein that facilitates the fusion of MVBs with autophagosomes to generate amphisomes.314

VAMP7: VAMP7 is a SNARE protein that colocalizes with Atg16L1 vesicles and phagophores, and is required, along with syntaxin 7, syntaxin 8 and Vti1b, for autophagosome formation.315 VAMP7 is also involved in the maturation of autophagosomes by facilitating fusion with the lysosome.314

VAMP8: A SNARE protein that, in conjunction with Vti1b, is needed for the fusion of autophagosomes with lysosomes.316

VCP (valosin-containing protein/p97): A AAA+-ATPase that is required for autophagosome maturation under basal conditions or when the proteasomal system is impaired; mutations of VCP result in the accumulation of immature, acidified autophagic vacuoles that contain ubiquitinated substrates.317,318 See also Cdc48.

Verteporfin: An FDA-approved drug; used in photodynamic therapy, but it inhibits the formation of autophagosomes in vivo without light activation.319

VMP1 (vacuole membrane protein 1): A membrane protein that localizes to the plasma membrane or the ER. Interacts with Beclin 1 and is required for macroautophagy.320,321

Vps34: The class III PtdIns 3-kinase that generates PtdIns(3) P, which is required for macroautophagy. In yeast, Vps34 is present in two complexes. Complex I consisting of Vps34, Vps15, Vps30/Atg6 and Atg14 is essential for macroautophagy. Complex II composed of Vps34, Vps15, Vps30/Atg6 and Vps38 acts in the vacuolar protein sorting (Vps) pathway. In mammalian cells there are at least three PtdIns 3-kinase complexes that include Vps34, Vps15, Atg14L and Beclin 1, and combinations of UVRAG, Ambra1 and/or Rubicon.

Vps38: A component of the class III PtdIns 3-kinase complex II, which directs it to function in the vacuolar protein sorting (Vps) pathway.

VSM (vacuolar sequestering membranes): Extensions/protrusions of the vacuole limiting membrane along the surface of peroxisomes that occur during micropexophagy.322

Vti1: A soluble SNARE that, together with Sec18/NSF, is needed for the fusion of autophagosomes with the vacuole.274 In mammalian cells, the SNARE proteins VAMP8 and Vti1b mediate the fusion of antimicrobial and canonical autophagosomes with lysosomes.323

WIPI (WD repeat protein interacting with phosphoinositides): The WIPI proteins are putative mammalian homologs of yeast Atg18 and Atg21. There are four WIPI proteins in mammalian cells. WIPI1/WIPI49 and WIPI2 localize with LC3 and bind PtdIns(3)P.324 WIPI2 is required for starvation-induced autophagy.325

wortmannin (WM): An inhibitor of PtdIns 3-kinases; it inhibits macroautophagy.201

WXXL motif: An amino acid sequence present in proteins that allows an interaction with Atg8/LC3; the consensus is W/YXXL/I. Also see AIM and LIR/LRS.326

WYE-354: A catalytic mTOR inhibitor that increases macroautophagic flux to a greater level than allosteric inhibitors such as rapamycin (and may be used to induce macroautophagy in cell lines that are resistant to rapamycin and its derivatives); short-term treatment with WYE-354 can inhibit both mTORC1 and mTORC2, but the effects on flux are due to the former.327 See also Ku-0063794.

XBP1: A component of the endoplasmic reticulum stress response that activates macroautophagy. The XBP1 yeast ortholog is Hac1.328

Xenophagy: Cell-autonomous innate immunity defense, whereby cells eliminate intracellular pathogens by capture into autophagosomes with subsequent killing.329

Xestospongin B: An antagonist of the IP3R (inositol-1,4,5trisphosphate receptor) that dissociates the inhibitory interaction between IP3R and Beclin 1 and induces macroautophagy.330

Ykt6: A prenylated vesicle SNARE involved in Golgi transport and fusion with the vacuole (including Cvt vesicle delivery to the vacuole331); temperature sensitive ykt6 mutations also prevent closure of the phagophore.273

Ypt1: A yeast GTP binding protein that functions in several forms of autophagy.306 Ypt1 is needed for correct localization of Atg8 to the PAS. See also TRAPPIII. The mammalian homolog, Rab1, is required for autophagosome formation and for autophagic targeting of Salmonella.332,333

Ypt7: A yeast homolog of Rab7, needed for the fusion of autophagosomes with the vacuole.

ZIPK (zipper-interacting protein kinase): See Sqa.334

zymophagy: The selective degradation of activated zymogen granules by macroautophagy in a process dependent on VMP1, p62 and the ubiquitin protease USP9x.335 See also crinophagy.


1. Seglen P, Gordon P. 3-Methyladenine: Specific inhibitor of autophagic/lysosomal protein degradation in isolated hepatocytes. Proc Natl Acad Sci USA. 1982;79:1889–1892. [PubMed]
2. Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 2010;285:10850, 10861. doi: 10.1074/jbc.M109.080796. [PMC free article] [PubMed] [Cross Ref]
3. Zhang N, Chen Y, Jiang R, Li E, Chen X, Xi Z, et al. PARP and RIP 1 are required for autophagy induced by 11′-deoxyverticillin A, which precedes caspase-dependent apoptosis. Autophagy. 2011;7:598–612. doi: 10.4161/auto.7.6.15103. [PubMed] [Cross Ref]
4. Radoshevich L, Murrow L, Chen N, Fernandez E, Roy S, Fung C, et al. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell. 2010;142:590–600. [PMC free article] [PubMed]
5. Pozuelo-Rubio M. Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase. Cell Death Differ. 2011;18:479–492. doi: 10.1038/cdd.2010.118. [PMC free article] [PubMed] [Cross Ref]
6. Shi CS, Kehrl JH. Traf6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci Signal. 2010;3:42. doi: 10.1126/scisignal.2000751. [PubMed] [Cross Ref]
7. Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, et al. Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1. EMBO J. 2007;26:2527–2539. doi: 10.1038/sj.emboj.7601689. [PubMed] [Cross Ref]
8. Haberman AS, Akbar MA, Ray S, Kramer H. Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking. Development. 2010;137:2157–2166. doi: 10.1242/dev.044230. [PubMed] [Cross Ref]
9. Bhutia SK, Kegelman TP, Das SK, Azab B, Su ZZ, Lee SG, et al. Astrocyte elevated gene-1 induces protective autophagy. Proc Natl Acad Sci USA. 2010;107:22243–22248. doi: 10.1073/pnas.1009479107. [PubMed] [Cross Ref]
10. Eby KG, Rosenbluth JM, Mays DJ, Marshall CB, Barton CE, Sinha S, et al. ISG20L1 is a p53 family target gene that modulates genotoxic stress-induced autophagy. Mol Cancer. 2010;9:95. doi: 10.1186/1476-4598-9-95. [PMC free article] [PubMed] [Cross Ref]
11. Øverbye A, Fengsrud M, Seglen PO. Proteomic analysis of membrane-associated proteins from rat liver autophagosomes. Autophagy. 2007;3:300–322. [PubMed]
12. Garcia-Marcos M, Ear J, Farquhar MG, Ghosh PA. GDI (AGS3) and a GEF (GIV) regulate autophagy by balancing G protein activity and growth factor signals. Mol Biol Cell. 2011;22:673–686. doi: 10.1091/mbc.E10-08-0738. [PMC free article] [PubMed] [Cross Ref]
13. Pattingre S, De Vries L, Bauvy C, Chantret I, Cluzeaud F, Ogier-Denis E, et al. The G-protein regulator AGS3 controls an early event during macroautophagy in human intestinal HT-29 cells. J Biol Chem. 2003;278:20995–21002. doi: 10.1074/jbc.M300917200. [PubMed] [Cross Ref]
14. Samari HR, Seglen PO. Inhibition of hepatocytic autophagy by adenosine, aminoimidazole-4-carboxamide riboside and N6-mercaptopurine riboside. Evidence for involvement of amp-activated protein kinase. J Biol Chem. 1998;273:23758–23763. doi: 10.1074/jbc.273.37.23758. [PubMed] [Cross Ref]
15. Viana R, Aguado C, Esteban I, Moreno D, Viollet B, Knecht E, et al. Role of AMP-activated protein kinase in autophagy and proteasome function. Biochem Biophys Res Commun. 2008;369:964–968. doi: 10.1016/j.bbrc.2008.02.126. [PubMed] [Cross Ref]
16. Meley D, Bauvy C, Houben-Weerts JH, Dubbelhuis PF, Helmond MT, Codogno P, et al. AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem. 2006;281:34870–34879. doi: 10.1074/jbc.M605488200. [PubMed] [Cross Ref]
17. Noda NN, Ohsumi Y, Inagaki F. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett. 2010;584:1379–1385. doi: 10.1016/j.febslet.2010.01.018. [PubMed] [Cross Ref]
18. Simonsen A, Birkeland HC, Gillooly DJ, Mizushima N, Kuma A, Yoshimori T, et al. Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci. 2004;117:4239–4251. doi: 10.1242/jcs.01287. [PubMed] [Cross Ref]
19. Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, Melia TJ, et al. The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010;38:265–279. doi: 10.1016/j.molcel.2010.04.007. [PMC free article] [PubMed] [Cross Ref]
20. Clausen TH, Lamark T, Isakson P, Finley K, Larsen KB, Brech A, et al. p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy. 2010;6:330–344. doi: 10.4161/auto.6.3.11226. [PubMed] [Cross Ref]
21. Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010;465:942–946. [PMC free article] [PubMed]
22. Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447:1121–1125. [PubMed]
23. Seglen PO, Berg TO, Blankson H, Fengsrud M, Holen I, Stromhaug PE. Structural aspects of autophagy. Adv Exp Med Biol. 1996;389:103–111. [PubMed]
24. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331:456–461. doi: 10.1126/science.1196371. [PMC free article] [PubMed] [Cross Ref]
25. Kim J, Kundu M, Viollet B, Guan K-L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132–141. doi: 10.1038/ncb2152. [PubMed] [Cross Ref]
26. Meijer AJ, Codogno P. AMP-activated protein kinase and autophagy. Autophagy. 2007;3:238–240. [PubMed]
27. Löffler AS, Alers S, Dieterle AM, Keppeler H, Franz-Wachtel M, Kundu M, et al. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011;7:696–706. doi: 10.4161/auto.7.7.15451. [PubMed] [Cross Ref]
28. Deretic V, Levine B. Autophagy, immunity and microbial adaptations. Cell Host Microbe. 2009;5:527–549. doi: 10.1016/j.chom.2009.05.016. [PMC free article] [PubMed] [Cross Ref]
29. Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, et al. ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway. Sci Signal. 2010;3:9. doi: 10.1126/scisignal.2000590. [PMC free article] [PubMed] [Cross Ref]
30. Klionsky DJ, Cregg J, Dunn WJ, Emr S, Sakai Y, Sandoval I, et al. A unified nomenclature for yeast autophagy-related genes. Dev Cell. 2003;5:539–545. doi: 10.1016/S1534-5807(03)00296-X. [PubMed] [Cross Ref]
31. Matsuura A, Tsukada M, Wada Y, Ohsumi Y. Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene. 1997;192:245–250. doi: 10.1016/S0378-1119(97)00084-X. [PubMed] [Cross Ref]
32. Wang C-W, Kim J, Huang W-P, Abeliovich H, Stromhaug PE, Dunn WA, Jr, et al. Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy and pexophagy pathways. J Biol Chem. 2001;276:30442–30451. doi: 10.1074/jbc.M102342200. [PMC free article] [PubMed] [Cross Ref]
33. Shintani T, Suzuki K, Kamada Y, Noda T, Ohsumi Y. Apg2p functions in autophagosome formation on the perivacuolar structure. J Biol Chem. 2001;276:30452–30460. doi: 10.1074/jbc.M102346200. [PubMed] [Cross Ref]
34. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, et al. A ubiquitin-like system mediates protein lipidation. Nature. 2000;408:488–492. doi: 10.1038/35044114. [PubMed] [Cross Ref]
35. Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M. AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae. J Bacteriol. 1997;179:1068–1076. [PMC free article] [PubMed]
36. Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, et al. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 2000;151:263–276. doi: 10.1083/jcb.151.2.263. [PMC free article] [PubMed] [Cross Ref]
37. Tanida I, Sou YS, Minematsu-Ikeguchi N, Ueno T, Kominami E. Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3. FEBS J. 2006;273:2553–2562. doi: 10.1111/j.1742-4658.2006.05260.x. [PubMed] [Cross Ref]
38. Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM. Kinetics comparisons of mammalian Atg4 homo-logs indicate selective preferences toward diverse Atg8 substrates. J Biol Chem. 2011;286:7327–7338. doi: 10.1074/jbc.M110.199059. [PMC free article] [PubMed] [Cross Ref]
39. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, et al. A protein conjugation system essential for autophagy. Nature. 1998;395:395–398. doi: 10.1038/26506. [PubMed] [Cross Ref]
40. Kametaka S, Okano T, Ohsumi M, Ohsumi Y. Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. J Biol Chem. 1998;273:22284–22291. doi: 10.1074/jbc.273.35.22284. [PubMed] [Cross Ref]
41. Tanida I, Mizushima N, Kiyooka M, Ohsumi M, Ueno T, Ohsumi Y, et al. Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy. Mol Biol Cell. 1999;10:1367–1379. [PMC free article] [PubMed]
42. Kim J, Dalton VM, Eggerton KP, Scott SV, Klionsky DJ. Apg7p/Cvt2p is required for the cytoplasm-tovacuole targeting, macroautophagy and peroxisome degradation pathways. Mol Biol Cell. 1999;10:1337–1351. [PMC free article] [PubMed]
43. Huang W-P, Scott SV, Kim J, Klionsky DJ. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 2000;275:5845–5851. doi: 10.1074/jbc.275.8.5845. [PubMed] [Cross Ref]
44. Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, et al. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999;147:435–446. doi: 10.1083/jcb.147.2.435. [PMC free article] [PubMed] [Cross Ref]
45. Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 2010;29:1792–1802. doi: 10.1038/emboj.2010.74. [PubMed] [Cross Ref]
46. Noda T, Kim J, Huang W-P, Baba M, Tokunaga C, Ohsumi Y, et al. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J Cell Biol. 2000;148:465–480. doi: 10.1083/jcb.148.3.465. [PMC free article] [PubMed] [Cross Ref]
47. Reggiori F, Shintani T, Nair U, Klionsky DJ. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy. 2005;1:101–109. [PMC free article] [PubMed]
48. Yamada T, Carson AR, Caniggia I, Umebayashi K, Yoshimori T, Nakabayashi K, et al. Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. J Biol Chem. 2005;280:18283–18290. doi: 10.1074/jbc.M413957200. [PubMed] [Cross Ref]
49. Shintani T, Mizushima N, Ogawa Y, Matsuura A, Noda T, Ohsumi Y. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J. 1999;18:5234–5241. doi: 10.1093/emboj/18.19.5234. [PubMed] [Cross Ref]
50. Kim J, Kamada Y, Stromhaug PE, Guan J, Hefner-Gravink A, Baba M, et al. Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. J Cell Biol. 2001;153:381–396. doi: 10.1083/jcb.153.2.381. [PMC free article] [PubMed] [Cross Ref]
51. Scott SV, Nice DC, III, Nau JJ, Weisman LS, Kamada Y, Keizer-Gunnink I, et al. Apg13p and Vac8p are part of a complex of phosphoproteins that are required for cytoplasm to vacuole targeting. J Biol Chem. 2000;275:25840–25849. doi: 10.1074/jbc.M002813200. [PubMed] [Cross Ref]
52. Funakoshi T, Matsuura A, Noda T, Ohsumi Y. Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae. Gene. 1997;192:207–213. doi: 10.1016/S03781119(97)00031-0. [PubMed] [Cross Ref]
53. Teter SA, Eggerton KP, Scott SV, Kim J, Fischer AM, Klionsky DJ. Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem. 2001;276:2083–2087. [PMC free article] [PubMed]
54. Epple UD, Suriapranata I, Eskelinen E-L, Thumm M. Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol. 2001;183:5942–5955. doi: 10.1128/JB.183.20.5942-55.2001. [PMC free article] [PubMed] [Cross Ref]
55. Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J. 1999;18:3888–3896. doi: 10.1093/emboj/18.14.3888. [PubMed] [Cross Ref]
56. Massey DC, Parkes M. Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn's disease. Autophagy. 2007;3:649–651. [PubMed]
57. Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, Ohsumi Y. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell. 2005;16:2544–2553. doi: 10.1091/mbc.E04-08-0669. [PMC free article] [PubMed] [Cross Ref]
58. Cheong H, Yorimitsu T, Reggiori F, Legakis JE, Wang C-W, Klionsky DJ. Atg17 regulates the magnitude of the autophagic response. Mol Biol Cell. 2005;16:3438–3453. doi: 10.1091/mbc.E04-10-0894. [PMC free article] [PubMed] [Cross Ref]
59. Guan J, Stromhaug PE, George MD, Habibzadegah-Tari P, Bevan A, Dunn WA, Jr, et al. Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy and autophagy in Saccharomyces cerevisiae and Pichia pastoris. Mol Biol Cell. 2001;12:3821–3838. [PMC free article] [PubMed]
60. Scott SV, Guan J, Hutchins MU, Kim J, Klionsky DJ. Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell. 2001;7:1131–1141. doi: 10.1016/S1097-2765(01)00263-5. [PMC free article] [PubMed] [Cross Ref]
61. Leber R, Silles E, Sandoval IV, Mazon MJ. Yol082p, a novel CVT protein involved in the selective targeting of aminopeptidase I to the yeast vacuole. J Biol Chem. 2001;276:29210–29217. doi: 10.1074/jbc.M101438200. [PubMed] [Cross Ref]
62. Nice DC, Sato TK, Stromhaug PE, Emr SD, Klionsky DJ. Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13 and Cvt20, to phosphatidylinositol-3-phosphate at the pre-autophagosomal structure is required for selective autophagy. J Biol Chem. 2002;277:30198–30207. doi: 10.1074/jbc.M204736200. [PMC free article] [PubMed] [Cross Ref]
63. Stromhaug PE, Reggiori F, Guan J, Wang C-W, Klionsky DJ. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol Biol Cell. 2004;15:3553–3566. doi: 10.1091/mbc.E04-02-0147. [PMC free article] [PubMed] [Cross Ref]
64. Yang Z, Huang J, Geng J, Nair U, Klionsky DJ. Atg22 recycles amino acids to link the degradative and recycling functions of autophagy. Mol Biol Cell. 2006;17:5094–5104. doi: 10.1091/mbc.E06-06-0479. [PMC free article] [PubMed] [Cross Ref]
65. Suriapranata I, Epple UD, Bernreuther D, Bredschneider M, Sovarasteanu K, Thumm M. The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci. 2000;113:4025–4033. [PubMed]
66. Legakis JE, Yen W-L, Klionsky DJ. A cycling protein complex required for selective autophagy. Autophagy. 2007;3:422–432. [PubMed]
67. Reggiori F, Tucker KA, Stromhaug PE, Klionsky DJ. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell. 2004;6:79–90. doi: 10.1016/S1534-5807(03)00402-7. [PubMed] [Cross Ref]
68. Tucker KA, Reggiori F, Dunn WA, Jr, Klionsky DJ. Atg23 is essential for the cytoplasm to vacuole targeting pathway and efficient autophagy but not pexophagy. J Biol Chem. 2003;278:48445–48452. doi: 10.1074/jbc.M309238200. [PMC free article] [PubMed] [Cross Ref]
69. Monastyrska I, Kiel JAKW, Krikken AM, Komduur JA, Veenhuis M, van der Klei IJ. The Hansenula polymorpha ATG25 gene encodes a novel coiled-coil protein that is required for macropexophagy. Autophagy. 2005;1:92–100. doi: 10.4161/auto.1.2.1832. [PubMed] [Cross Ref]
70. Cao Y, Klionsky DJ. Atg26 is not involved in autophagy-related pathways in Saccharomyces cerevisiae. Autophagy. 2007;3:17–20. [PubMed]
71. Yamashita S, Oku M, Wasada Y, Ano Y, Sakai Y. PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy. J Cell Biol. 2006;173:709–717. doi: 10.1083/jcb.200512142. [PMC free article] [PubMed] [Cross Ref]
72. Yen W-L, Legakis JE, Nair U, Klionsky DJ. Atg27 is required for autophagy-dependent cycling of Atg9. Mol Biol Cell. 2007;18:581–593. doi: 10.1091/mbc.E06-07-0612. [PMC free article] [PubMed] [Cross Ref]
73. Stasyk OV, Stasyk OG, Mathewson RD, Farre JC, Nazarko VY, Krasovska OS, et al. Atg28, a novel coiled-coil protein involved in autophagic degradation of peroxisomes in the methylotrophic yeast Pichia pastoris. Autophagy. 2006;2:30–38. [PubMed]
74. Kawamata T, Kamada Y, Suzuki K, Kuboshima N, Akimatsu H, Ota S, et al. Characterization of a novel autophagy-specific gene, ATG29. Biochem Biophys Res Commun. 2005;338:1884–1889. doi: 10.1016/j.bbrc.2005.10.163. [PubMed] [Cross Ref]
75. Farré JC, Manjithaya R, Mathewson RD, Subramani S. PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell. 2008;14:365–376. doi: 10.1016/j.devcel.2007.12.011. [PubMed] [Cross Ref]
76. Kabeya Y, Kawamata T, Suzuki K, Ohsumi Y. Cis1/Atg31 is required for autophagosome formation in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2007;356:405–410. doi: 10.1016/j.bbrc.2007.02.150. [PubMed] [Cross Ref]
77. Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell. 2009;17:98–109. doi: 10.1016/j.devcel.2009.06.014. [PMC free article] [PubMed] [Cross Ref]
78. Okamoto K, Kondo-Okamoto N, Ohsumi Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell. 2009;17:87–97. doi: 10.1016/j.devcel.2009.06.013. [PubMed] [Cross Ref]
79. Kanki T, Wang K, Baba M, Bartholomew CR, Lynch-Day MA, Du Z, et al. A genomic screen for yeast mutants defective in selective mitochondria autophagy. Mol Biol Cell. 2009;20:4730–4738. doi: 10.1091/mbc.E09-03-0225. [PMC free article] [PubMed] [Cross Ref]
80. Watanabe Y, Noda NN, Kumeta H, Suzuki K, Ohsumi Y, Inagaki F. Selective transport of α-mannosidase by autophagic pathways: structural basis for cargo recognition by Atg19 and Atg34. J Biol Chem. 2010;285:30026–30033. doi: 10.1074/jbc.M110.143545. [PMC free article] [PubMed] [Cross Ref]
81. Meijer WH, van der Klei IJ, Veenhuis M, Kiel JAKW. ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy. 2007;3:106–116. [PubMed]
82. Nazarko VY, Nazarko TY, Farre JC, Stasyk OV, Warnecke D, Ulaszewski S, et al. Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus formation in Pichia pastoris. Autophagy. 2011;7:375–385. doi: 10.4161/auto.7.4.14369. [PMC free article] [PubMed] [Cross Ref]
83. Hosokawa N, Sasaki T, Iemura S, Natsume T, Hara T, Mizushima N. Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy. 2009;5:973–979. doi: 10.4161/auto.5.7.9296. [PubMed] [Cross Ref]
84. Mercer CA, Kaliappan A, Dennis PB. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy. 2009;5:649–662. doi: 10.4161/auto.5.5.8249. [PubMed] [Cross Ref]
85. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, Maclean KH, et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA. 2010;107:4153–4158. doi: 10.1073/pnas.0913860107. [PubMed] [Cross Ref]
86. Dunn WA., Jr Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol. 1990;110:1935–1945. doi: 10.1083/jcb.110.6.1935. [PMC free article] [PubMed] [Cross Ref]
87. Baba M, Osumi M, Ohsumi Y. Analysis of the membrane structures involved in autophagy in yeast by freeze-replica method. Cell Struct Funct. 1995;20:465–471. doi: 10.1247/csf.20.465. [PubMed] [Cross Ref]
88. Chu CT. Autophagic stress in neuronal injury and disease. J Neuropathol Exp Neurol. 2006;65:423–432. doi: 10.1097/ [PMC free article] [PubMed] [Cross Ref]
89. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct. 1998;23:33–42. doi: 10.1247/csf.23.33. [PubMed] [Cross Ref]
90. Klionsky DJ, Elazar Z, Seglen PO, Rubinsztein DC. Does bafilomycin A1 block the fusion of autophagosomes with lysosomes? Autophagy. 2008;4:849–950. [PubMed]
91. Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C. BAG3 mediates chaperone-based aggresometargeting and selective autophagy of misfolded proteins. EMBO Rep. 2011;12:149–156. doi: 10.1038/embor.2010.203. [PubMed] [Cross Ref]
92. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol-3-kinase. Proc Natl Acad Sci USA. 2008;105:19211–19216. doi: 10.1073/pnas.0810452105. [PubMed] [Cross Ref]
93. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25:717–729. doi: 10.1101/gad.2016111. [PubMed] [Cross Ref]
94. Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25:460–470. doi: 10.1101/gad.2016311. [PubMed] [Cross Ref]
95. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L) Proc Natl Acad Sci USA. 2011;108:7769–7774. doi: 10.1073/pnas.1016472108. [PubMed] [Cross Ref]
96. Manjithaya R, Jain S, Farre JC, Subramani S. A yeast MAPK cascade regulates pexophagy but not other autophagy pathways. J Cell Biol. 2010;189:303–310. doi: 10.1083/jcb.200909154. [PMC free article] [PubMed] [Cross Ref]
97. Mao K, Zhao M, Xu T, Klionsky DJ. Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol. 2011;193:755–767. doi: 10.1083/jcb.201102092. [PMC free article] [PubMed] [Cross Ref]
98. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672–676. doi: 10.1038/45257. [PubMed] [Cross Ref]
99. Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007;9:1142–1151. doi: 10.1038/ncb1634. [PMC free article] [PubMed] [Cross Ref]
100. Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA, et al. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ. 2007;14:146–157. doi: 10.1038/sj.cdd.4401936. [PubMed] [Cross Ref]
101. Daido S, Kanzawa T, Yamamoto A, Takeuchi H, Kondo Y, Kondo S. Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res. 2004;64:4286–4293. doi: 10.1158/0008-5472.CAN-03-3084. [PubMed] [Cross Ref]
102. Ikeda H, Hideshima T, Fulciniti M, Perrone G, Mimura N, Yasui H, et al. PI3K/p110δ is a novel therapeutic target in multiple myeloma. Blood. 2010;116:1460–1468. doi: 10.1182/blood2009-06-222943. [PubMed] [Cross Ref]
103. Xia HG, Zhang L, Chen G, Zhang T, Liu J, Jin M, et al. Control of basal autophagy by calpain1 mediated cleavage of ATG5. Autophagy. 2010;6:616. doi: 10.4161/auto.6.1.10326. [PMC free article] [PubMed] [Cross Ref]
104. Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem. 2005;280:29060–29066. doi: 10.1074/jbc.M503824200. [PubMed] [Cross Ref]
105. Høyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-b and Bcl-2. Mol Cell. 2007;25:193–205. doi: 10.1016/j.molcel.2006.12.009. [PubMed] [Cross Ref]
106. Demarchi F, Bertoli C, Copetti T, Tanida I, Brancolini C, Eskelinen E-L, et al. Calpain is required for macroautophagy in mammalian cells. J Cell Biol. 2006;175:595–605. doi: 10.1083/jcb.200601024. [PMC free article] [PubMed] [Cross Ref]
107. Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010;20:143–148. doi: 10.1016/j.cub.2009.11.022. [PubMed] [Cross Ref]
108. Norman JM, Cohen GM, Bampton ET. The in vitro cleavage of the hAtg proteins by cell death proteases. Autophagy. 2010;6:1042–1056. doi: 10.4161/auto.6.8.13337. [PubMed] [Cross Ref]
109. Krick R, Bremer S, Welter E, Schlotterhose P, Muehe Y, Eskelinen E-L, et al. Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J Cell Biol. 2010;190:965–973. doi: 10.1083/jcb.201002075. [PMC free article] [PubMed] [Cross Ref]
110. Joubert PE, Meiffren G, Gregoire IP, Pontini G, Richetta C, Flacher M, et al. Autophagy induction by the pathogen receptor CD46. Cell Host Microbe. 2009;6:354–366. doi: 10.1016/j.chom.2009.09.006. [PubMed] [Cross Ref]
111. Cuervo AM. Chaperone-mediated autophagy: selectivity pays off. Trends Endocrinol Metab. 2010;21:142–150. doi: 10.1016/j.tem.2009.10.003. [PMC free article] [PubMed] [Cross Ref]
112. Dice JF. Chaperone-mediated autophagy. Autophagy. 2007;3:295–299. [PubMed]
113. Agarraberes FA, Terlecky S, Dice J. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol. 1997;137:825–834. doi: 10.1083/jcb.137.4.825. [PMC free article] [PubMed] [Cross Ref]
114. Cuervo AM, Dice J. A receptor for the selective uptake and degradation of proteins by lysosomes. Science. 1996;273:501–503. doi: 10.1126/science.273.5274.501. [PubMed] [Cross Ref]
115. Fedorko M. Effect of chloroquine on morphology of cytoplasmic granules in maturing human leukocytes—an ultrastructural study. J Clin Invest. 1967;46:1932–1942. doi: 10.1172/JCI105683. [PMC free article] [PubMed] [Cross Ref]
116. Yogev O, Goldberg R, Anzi S, Shaulian E. Jun proteins are starvation-regulated inhibitors of autophagy. Cancer Res. 2010;70:2318–2327. doi: 10.1158/0008-5472.CAN-09-3408. [PubMed] [Cross Ref]
117. Yang Z, Geng J, Yen W-L, Wang K, Klionsky DJ. Positive or negative regulatory roles of different cyclindependent kinase Pho85-cyclin complexes orchestrate induction of autophagy in Saccharomyces cerevisiae. Mol Cell. 2010;38:250–264. doi: 10.1016/j.molcel.2010.02.033. [PMC free article] [PubMed] [Cross Ref]
118. Yen W-L, Shintani T, Nair U, Cao Y, Richardson BC, Li Z, et al. The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy. J Cell Biol. 2010;188:101–114. doi: 10.1083/jcb.200904075. [PMC free article] [PubMed] [Cross Ref]
119. Smith RE, Farquhar MG. Lysosome function in the regulation of the secretory process in cells of the anterior pituitary gland. J Cell Biol. 1966;31:319–347. doi: 10.1083/jcb.31.2.319. [PMC free article] [PubMed] [Cross Ref]
120. Ponpuak M, Davis AS, Roberts EA, Delgado MA, Dinkins C, Zhao Z, et al. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity. 2010;32:329–341. doi: 10.1016/j.immuni.2010.02.009. [PMC free article] [PubMed] [Cross Ref]
121. Wang M, Tan W, Zhou J, Leow J, Go M, Lee HS, et al. A small molecule inhibitor of isoprenylcysteine carboxymethyltransferase induces autophagic cell death in PC3 prostate cancer cells. J Biol Chem. 2008;283:18678–18684. doi: 10.1074/jbc.M801855200. [PubMed] [Cross Ref]
122. Harding TM, Morano KA, Scott SV, Klionsky DJ. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995;131:591–602. doi: 10.1083/jcb.131.3.591. [PMC free article] [PubMed] [Cross Ref]
123. Koren I, Reem E, Kimchi A. DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol. 2010;20:1093–1098. doi: 10.1016/j.cub.2010.04.041. [PubMed] [Cross Ref]
124. Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol. 2002;157:455–468. doi: 10.1083/jcb.200109094. [PMC free article] [PubMed] [Cross Ref]
125. Köhler K, Brunner E, Guan XL, Boucke K, Greber UF, Mohanty S, et al. A combined proteomic and genetic analysis identifies a role for the lipid desaturase Desat1 in starvation-induced autophagy in Drosophila. Autophagy. 2009;5:980–990. doi: 10.4161/auto.5.7.9325. [PubMed] [Cross Ref]
126. Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol-3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182:685–701. doi: 10.1083/jcb.200803137. [PMC free article] [PubMed] [Cross Ref]
127. Shahnazari S, Yen W-L, Birmingham CL, Shiu J, Namolovan A, Zheng YT, et al. A diacylglyceroldependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host Microbe. 2010;8:137–146. doi: 10.1016/j.chom.2010.07.002. [PubMed] [Cross Ref]
128. Ren H, Fu K, Mu C, Li B, Wang D, Wang G. DJ-1, a cancer and Parkinson's disease associated protein, regulates autophagy through JNK pathway in cancer cells. Cancer Lett. 2010;297:101–108. doi: 10.1016/j.canlet.2010.05.001. [PubMed] [Cross Ref]
129. Mauvezin C, Orpinell M, Francis VA, Mansilla F, Duran J, Ribas V, et al. The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells. EMBO Rep. 2010;11:37–44. doi: 10.1038/embor.2009.242. [PubMed] [Cross Ref]
130. Crighton D, Wilkinson S, O'Prey J, Syed N, Smith P, Harrison PR, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126:121–134. doi: 10.1016/j.cell.2006.05.034. [PubMed] [Cross Ref]
131. McPhee CK, Logan MA, Freeman MR, Baehrecke EH. Activation of autophagy during cell death requires the engulfment receptor Draper. Nature. 2010;465:1093–1096. [PMC free article] [PubMed]
132. Tambe Y, Yamamoto A, Isono T, Chano T, Fukuda M, Inoue H. The drs tumor suppressor is involved in the maturation process of autophagy induced by low serum. Cancer Lett. 2009;283:74–83. doi: 10.1016/j.canlet.2009.03.028. [PubMed] [Cross Ref]
133. Polager S, Ofir M, Ginsberg D. E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene. 2008;27:4860–4864. doi: 10.1038/onc.2008.117. [PubMed] [Cross Ref]
134. Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM. Identification of regulators of chaperone-mediated autophagy. Mol Cell. 2010;39:535–547. doi: 10.1016/j.molcel.2010.08.004. [PMC free article] [PubMed] [Cross Ref]
135. Tallóczy Z, Jiang W, Virgin HW, IV, Leib DA, Scheuner D, Kaufman RJ, et al. Regulation of starvation- and virus-induced autophagy by the eIF2a kinase signaling pathway. Proc Natl Acad Sci USA. 2002;99:190–195. doi: 10.1073/pnas.012485299. [PubMed] [Cross Ref]
136. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, et al. ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 2007;14:230–239. doi: 10.1038/sj.cdd.4401984. [PubMed] [Cross Ref]
137. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, et al. Microautophagy of cytosolic proteins by late endosomes. Dev Cell. 2011;20:131–139. doi: 10.1016/j.devcel.2010.12.003. [PMC free article] [PubMed] [Cross Ref]
138. Tian Y, Li Z, Hu W, Ren H, Tian E, Zhao Y, et al. C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell. 2010;141:1042–1055. doi: 10.1016/j.cell.2010.04.034. [PubMed] [Cross Ref]
139. Tian E, Wang F, Han J, Zhang H. epg-1 functions in autophagy-regulated processes and may encode a highly divergent Atg13 homolog in C. elegans. Autophagy. 2009;5:608–615. doi: 10.4161/auto.5.5.8624. [PubMed] [Cross Ref]
140. Ogier-Denis E, Pattingre S, El Benna J, Codogno P. Erk1/2-dependent phosphorylation of Ga-interacting protein stimulates its GTPase accelerating activity and autophagy in human colon cancer cells. J Biol Chem. 2000;275:39090–39095. doi: 10.1074/jbc.M006198200. [PubMed] [Cross Ref]
141. Zhu JH, Horbinski C, Guo F, Watkins S, Uchiyama Y, Chu CT. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl4-phenylpyridinium-induced cell death. Am J Pathol. 2007;170:75–86. doi: 10.2353/ajpath.2007.060524. [PubMed] [Cross Ref]
142. Dagda RK, Zhu J, Kulich SM, Chu CT. Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson's disease. Autophagy. 2008;4:770–782. [PMC free article] [PubMed]
143. Bodemann BO, Orvedahl A, Cheng T, Ram RR, Ou YH, Formstecher E, et al. RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell. 2011;144:253–267. doi: 10.1016/j.cell.2010.12.018. [PMC free article] [PubMed] [Cross Ref]
144. Abrahamsen H, Stenmark H. Protein secretion: unconventional exit by exophagy. Curr Biol. 2010;20:415–418. doi: 10.1016/j.cub.2010.03.011. [PubMed] [Cross Ref]
145. Manjithaya R, Anjard C, Loomis WF, Subramani S. Unconventional secretion of Pichia pastoris Acb1 is dependent on GRASP protein, peroxisomal functions and autophagosome formation. J Cell Biol. 2010;188:537–446. doi: 10.1083/jcb.200911149. [PMC free article] [PubMed] [Cross Ref]
146. Duran JM, Anjard C, Stefan C, Loomis WF, Malhotra V. Unconventional secretion of Acb1 is mediated by autophagosomes. J Cell Biol. 2010;188:527–536. doi: 10.1083/jcb.200911154. [PMC free article] [PubMed] [Cross Ref]
147. Iorio F, Bosotti R, Scacheri E, Belcastro V, Mithbaokar P, Ferriero R, et al. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci USA. 2010;107:14621–14626. doi: 10.1073/pnas.1000138107. [PubMed] [Cross Ref]
148. Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan J-L, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181:497–510. doi: 10.1083/jcb.200712064. [PMC free article] [PubMed] [Cross Ref]
149. Romano S, D'Angelillo A, Pacelli R, Staibano S, De Luna E, Bisogni R, et al. Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells. Cell Death Differ. 2010;17:145–157. doi: 10.1038/cdd.2009.115. [PubMed] [Cross Ref]
150. Huett A, Ng A, Cao Z, Kuballa P, Komatsu M, Daly MJ, et al. A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. J Immunol. 2009;182:4917–4930. doi: 10.4049/jimmunol.0803050. [PMC free article] [PubMed] [Cross Ref]
151. Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol. 2010;12:665–675. doi: 10.1038/ncb2069. [PubMed] [Cross Ref]
152. Hariharan N, Maejima Y, Nakae J, Paik J, Depinho RA, Sadoshima J. Deacetylation of FoxO by Sirt1 plays an essential role in mediating starvation-induced autophagy in cardiac myocytes. Circ Res. 2010;107:1470–1482. doi: 10.1161/CIRCRESAHA.110.227371. [PMC free article] [PubMed] [Cross Ref]
153. Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007;6:472–483. doi: 10.1016/j.cmet.2007.11.004. [PubMed] [Cross Ref]
154. Attaix D, Bechet D. FoxO3 controls dangerous proteolytic liaisons. Cell Metab. 2007;6:425–427. doi: 10.1016/j.cmet.2007.11.005. [PubMed] [Cross Ref]
155. Pankiv S, Alemu EA, Brech A, Bruun JA, Lamark T, Øvervatn A, et al. FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. J Cell Biol. 2010;188:253–269. doi: 10.1083/jcb.200907015. [PMC free article] [PubMed] [Cross Ref]
156. Ogier-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, et al. A heterotrimeric Gi3protein controls autophagic sequestration in the human colon cancer cell line HT-29. J Biol Chem. 1995;270:13–16. doi: 10.1074/jbc.270.1.13. [PubMed] [Cross Ref]
157. Ogier-Denis E, Houri JJ, Bauvy C, Codogno P. Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J Biol Chem. 1996;271:28593–28600. doi: 10.1074/jbc.271.45.28593. [PubMed] [Cross Ref]
158. Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, et al. Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. Brain Res Mol. 2000;85:1–12. doi: 10.1016/S0169-328X(00)00218-7. [PubMed] [Cross Ref]
159. Tanida I, Tanida-Miyake E, Ueno T, Kominami E. The human homolog of Saccharomyces cerevisiae Apg7p is a protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP and MAP-LC3. J Biol Chem. 2001;276:1701–1706. [PubMed]
160. Uddin MN, Ito S, Nishio N, Suganya T, Isobe KI. Gadd34 induces autophagy through the suppression of the mTOR pathway during starvation. Biochem Biophys Res Commun. 2011;407:692–698. [PubMed]
161. Ogier-Denis E, Petiot A, Bauvy C, Codogno P. Control of the expression and activity of the Ga-interacting protein (GAIP) in human intestinal cells. J Biol Chem. 1997;272:24599–24603. doi: 10.1074/jbc.272.39.24599. [PubMed] [Cross Ref]
162. Todd LR, Damin MN, Gomathinayagam R, Horn SR, Means AR, Sankar U. Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and function in mouse embryonic stem cells. Mol Biol Cell. 2010;21:1225–1236. doi: 10.1091/mbc.E09-11-0937. [PMC free article] [PubMed] [Cross Ref]
163. Li B, Castano AP, Hudson TE, Nowlin BT, Lin S-L, Bonventre JV, et al. The melanoma-associated trans-membrane glycoprotein Gpnmb controls trafficking of cellular debris for degradation and is essential for tissue repair. FASEB J. 2010;24:4767–4781. doi: 10.1096/fj.10-154757. [PubMed] [Cross Ref]
164. Iwata A, Riley BE, Johnston JA, Kopito RR. HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem. 2005;280:40282–40292. doi: 10.1074/jbc.M508786200. [PubMed] [Cross Ref]
165. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J. 2010;29:969–980. doi: 10.1038/emboj.2009.405. [PubMed] [Cross Ref]
166. Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 2007;447:859–863. doi: 10.1038/nature05853. [PubMed] [Cross Ref]
167. Mellor HR, Harris AL. The role of the hypoxiainducible BH3-only proteins BNIP3 and BNIP3L in cancer. Cancer Metastasis Rev. 2007;26:553–566. doi: 10.1007/s10555-007-9080-0. [PubMed] [Cross Ref]
168. Bohensky J, Shapiro IM, Leshinsky S, Terkhorn SP, Adams CS, Srinivas V. HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic pathway. Autophagy. 2007;3:207–214. [PubMed]
169. Tang D, Kang R, Livesey KM, Cheh CW, Farkas AA, Loughran P, et al. Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010;190:881–892. doi: 10.1083/jcb.200911078. [PMC free article] [PubMed] [Cross Ref]
170. Tang D, Kang R, Cheh CW, Livesey KM, Liang X, Schapiro NE, et al. HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene. 2010;29:5299–5310. doi: 10.1038/onc.2010.261. [PMC free article] [PubMed] [Cross Ref]
171. Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A. Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death Differ. 2009;16:175–183. doi: 10.1038/cdd.2008.143. [PMC free article] [PubMed] [Cross Ref]
172. Chiang H-L, Terlecky SR, Plant CP, Dice JF. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science. 1989;246:382–385. doi: 10.1126/science.2799391. [PubMed] [Cross Ref]
173. Kaushik S, Massey AC, Cuervo AM. Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated autophagy. EMBO J. 2006;25:3921–3933. doi: 10.1038/sj.emboj.7601283. [PubMed] [Cross Ref]
174. Bandyopadhyay U, Kaushik S, Vartikovsky L, Cuervo AM. Dynamic organization of the receptor for chaperone-mediated autophagy at the lysosomal membrane. Mol Cell Biol. 2008;28:5747–5763. doi: 10.1128/MCB.02070-07. [PMC free article] [PubMed] [Cross Ref]
175. Orvedahl A, Alexander D, Tallóczy Z, Sun Q, Wei Y, Zhang W, et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe. 2007;1:23–35. doi: 10.1016/j.chom.2006.12.001. [PubMed] [Cross Ref]
176. Criollo A, Senovilla L, Authier H, Maiuri MC, Morselli E, Vitale I, et al. The IKK complex contributes to the induction of autophagy. EMBO J. 2010;29:619–631. doi: 10.1038/emboj.2009.364. [PubMed] [Cross Ref]
177. Blanchet FP, Moris A, Nikolic DS, Lehmann M, Cardinaud S, Stalder R, et al. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity. 2010;32:654–669. doi: 10.1016/j.immuni.2010.04.011. [PMC free article] [PubMed] [Cross Ref]
178. Deretic V. Autophagy in innate and adaptive immunity. Trends Immunol. 2005;26:523–528. doi: 10.1016/ [PubMed] [Cross Ref]
179. Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol. 2005;170:1101–1111. doi: 10.1083/jcb.200504035. [PMC free article] [PubMed] [Cross Ref]
180. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science. 2006;313:1438–1441. doi: 10.1126/science.1129577. [PubMed] [Cross Ref]
181. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30:678–688. doi: 10.1016/j.molcel.2008.06.001. [PMC free article] [PubMed] [Cross Ref]
182. Vergne I, Roberts E, Elmaoued RA, Tosch V, Delgado MA, Proikas-Cezanne T, et al. Control of autophagy initiation by phosphoinositide-3-phosphatase Jumpy. EMBO J. 2009;28:2244–2258. doi: 10.1038/emboj.2009.159. [PubMed] [Cross Ref]
183. Nyfeler B, Bergman P, Triantafellow E, Wilson CJ, Zhu Y, Radetich B, et al. Relieving autophagy and 4EBP1 from rapamycin resistance. Mol Cell Biol. 2011;31:2867–2876. doi: 10.1128/MCB.05430-11. [PMC free article] [PubMed] [Cross Ref]
184. Aguado C, Sarkar S, Korolchuk VI, Criado O, Vernia S, Boya P, et al. Laforin, the most common protein mutated in Lafora disease, regulates autophagy. Hum Mol Genet. 2010;19:2867–2876. doi: 10.1093/hmg/ddq190. [PMC free article] [PubMed] [Cross Ref]
185. Eskelinen E-L, Cuervo AM, Taylor MR, Nishino I, Blum JS, Dice JF, et al. Unifying nomenclature for the isoforms of the lysosomal membrane protein LAMP-2. Traffic. 2005;6:1058–1061. doi: 10.1111/j.1600-0854.2005.00337.x. [PubMed] [Cross Ref]
186. Eskelinen E-L, Illert A, Tanaka Y, Schwarzmann G, Blanz J, Von Figura K, et al. Role of LAMP-2 in lysosome biogenesis and autophagy. Mol Biol Cell. 2002;13:3355–3368. [PMC free article] [PubMed]
187. Eskelinen E-L, Schmidt C, Neu S, Willenborg M, Fuertes G, Salvador N, et al. Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell. 2004;15:3132–3145. doi: 10.1091/mbc.E04-02-0103. [PMC free article] [PubMed] [Cross Ref]
188. Tanaka Y, Guhde G, Suter A, Eskelinen E-L, Hartmann D, Lullmann-Rauch R, et al. Accumulation of autophagic vacuoles and cardiomyopathy in Lamp-2-deficient mice. Nature. 2000;406:902–906. doi: 10.1038/35022595. [PubMed] [Cross Ref]
189. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homo-log of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–5728. doi: 10.1093/emboj/19.21.5720. [PubMed] [Cross Ref]
190. Cherra SJ, III, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, Day BW, et al. Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol. 2010;190:533–539. doi: 10.1083/jcb.201002108. [PMC free article] [PubMed] [Cross Ref]
191. Sanjuan MA, Dillon CP, Tait SW, Moshiach S, Dorsey F, Connell S, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450:1253–1257. doi: 10.1038/nature06421. [PubMed] [Cross Ref]
192. Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458:1131–1135. doi: 10.1038/nature07976. [PMC free article] [PubMed] [Cross Ref]
193. Kirkin V, Lamark T, Sou YS, Bjørkøy G, Nunn JL, Bruun JA, et al. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009;33:505–516. doi: 10.1016/j.molcel.2009.01.020. [PubMed] [Cross Ref]
194. Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol. 2007;9:218–224. doi: 10.1038/ncb1537. [PubMed] [Cross Ref]
195. Klionsky DJ, Cuervo AM, Seglen PO. Methods for monitoring autophagy from yeast to human. Autophagy. 2007;3:181–206. [PubMed]
196. Shang L, Chen S, Du F, Li S, Zhao L, Wang X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci USA. 2011;108:4788–4793. doi: 10.1073/pnas.1100844108. [PubMed] [Cross Ref]
197. Carew JS, Espitia CM, Esquivel JA, II, Mahalingam D, Kelly KR, Reddy G, et al. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011;286:6602–6613. doi: 10.1074/jbc.M110.151324. [PMC free article] [PubMed] [Cross Ref]
198. Plowey ED, Cherra SJ, III, Liu YJ, Chu CT. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem. 2008;105:1048–1056. doi: 10.1111/j.1471-4159.2008.05217.x. [PMC free article] [PubMed] [Cross Ref]
199. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet. 2009;18:4022–4034. doi: 10.1093/hmg/ddp346. [PMC free article] [PubMed] [Cross Ref]
200. Ng ACY, Eisenberg JM, Heath RJW, Huett A, Robinson CM, Nau GJ, et al. Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity. Proc Natl Acad Sci USA. 2011;108:4631–4638. doi: 10.1073/pnas.1000093107. [PubMed] [Cross Ref]
201. Blommaart EF, Krause U, Schellens JP, Vreeling-Sindelarova H, Meijer AJ. The phosphatidylinositol3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem. 1997;243:240–246. doi: 10.1111/j.1432-033.1997.0240a.x. [PubMed] [Cross Ref]
202. Biederbick A, Kern HF, Elsasser HP. Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles. Eur J Cell Biol. 1995;66:3–14. [PubMed]
203. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008;4:151–175. [PMC free article] [PubMed]
204. Oku M, Warnecke D, Noda T, Muller F, Heinz E, Mukaiyama H, et al. Peroxisome degradation requires catalytically active sterol glucosyltransferase with a GRAM domain. EMBO J. 2003;22:3231–3241. doi: 10.1093/emboj/cdg331. [PubMed] [Cross Ref]
205. Lemasters JJ. Selective mitochondrial autophagy or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction and aging. Rejuvenation Res. 2005;8:3–5. doi: 10.1089/rej.2005.8.3. [PubMed] [Cross Ref]
206. Taguchi-Atarashi N, Hamasaki M, Matsunaga K, Omori H, Ktistakis NT, Yoshimori T, et al. Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy. Traffic. 2010;11:468–478. doi: 10.1111/j.1600-0854.2010.01034.x. [PubMed] [Cross Ref]
207. Huang J, Canadien V, Lam GY, Steinberg BE, Dinauer MC, Magalhaes MA, et al. Activation of antibacterial autophagy by NADPH oxidases. Proc Natl Acad Sci USA. 2009;106:6226–6231. doi: 10.1073/pnas.0811045106. [PubMed] [Cross Ref]
208. Chang NC, Nguyen M, Germain M, Shore GC. Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 2010;29:606–618. doi: 10.1038/emboj.2009.369. [PubMed] [Cross Ref]
209. Chen YF, Kao CH, Chen YT, Wang CH, Wu CY, Tsai CY, et al. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 2009;23:1183–1194. doi: 10.1101/gad.1779509. [PubMed] [Cross Ref]
210. Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitincoated bacteria. Nat Immunol. 2009;10:1215–1221. doi: 10.1038/ni.1800. [PubMed] [Cross Ref]
211. Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008;135:1311–1323. doi: 10.1016/j.cell.2008.10.044. [PMC free article] [PubMed] [Cross Ref]
212. Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK, et al. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest. 2010;120:1310–1323. doi: 10.1172/JCI39987. [PMC free article] [PubMed] [Cross Ref]
213. Djavaheri-Mergny M, Amelotti M, Mathieu J, Besancon F, Bauvy C, Codogno P. Regulation of autophagy by NFκB transcription factor and reactives oxygen species. Autophagy. 2007;3:390–392. [PubMed]
214. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA. 2007;104:19500–19505. doi: 10.1073/pnas.0708818104. [PubMed] [Cross Ref]
215. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhaes JG, et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol. 2010;11:55–62. doi: 10.1038/ni.1823. [PubMed] [Cross Ref]
216. Scarlatti F, Maffei R, Beau I, Ghidoni R, Codogno P. Non-canonical autophagy: an exception or an underestimated form of autophagy? Autophagy. 2008;4:1083–1085. [PubMed]
217. Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T, et al. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature. 2009;461:654–658. doi: 10.1038/nature08455. [PubMed] [Cross Ref]
218. Itoh T, Kanno E, Uemura T, Waguri S, Fukuda M. OATL1, a novel autophagosome-resident Rab33BGAP, regulates autophagosomal maturation. J Cell Biol. 2011;192:839–853. doi: 10.1083/jcb.201008107. [PMC free article] [PubMed] [Cross Ref]
219. Li B, Hu Q, Wang H, Man N, Ren H, Wen L, et al. Omi/HtrA2 is a positive regulator of autophagy that facilitates the degradation of mutant proteins involved in neurodegenerative diseases. Cell Death Differ. 2010;17:1773–1784. doi: 10.1038/cdd.2010.55. [PubMed] [Cross Ref]
220. Kong DK, Georgescu SP, Cano C, Aronovitz MJ, Iovanna JL, Patten RD, et al. Deficiency of the transcriptional regulator p8 results in increased autophagy and apoptosis, and causes impaired heart function. Mol Biol Cell. 2010;21:1335–1349. doi: 10.1091/mbc.E09-09-0818. [PMC free article] [PubMed] [Cross Ref]
221. Webber JL, Tooze SA. Coordinated regulation of autophagy by p38α MAPK through mAtg9 and p38IP. EMBO J. 2010;29:27–40. doi: 10.1038/emboj.2009.321. [PubMed] [Cross Ref]
222. Tavernarakis N, Pasparaki A, Tasdemir E, Maiuri MC, Kroemer G. The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy. 2008;4:870–873. [PubMed]
223. Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Øvervatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171:603–614. doi: 10.1083/jcb.200507002. [PMC free article] [PubMed] [Cross Ref]
224. Dou Z, Chattopadhyay M, Pan JA, Guerriero JL, Jiang YP, Ballou LM, et al. The class IA phosphatidylinositol3-kinase p110β subunit is a positive regulator of autophagy. J Cell Biol. 2010;191:827–843. doi: 10.1083/jcb.201006056. [PMC free article] [PubMed] [Cross Ref]
225. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183:795–803. doi: 10.1083/jcb.200809125. [PMC free article] [PubMed] [Cross Ref]
226. Shi G, Lee JR, Grimes DA, Racacho L, Ye D, Yang H, et al. Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease. Hum Mol Genet. 2011;20:1966–1974. [PubMed]
227. Muñoz-Gámez JA, Rodriguez-Vargas JM, Quiles-Perez R, Aguilar-Quesada R, Martin-Oliva D, de Murcia G, et al. PARP-1 is involved in autophagy induced by DNA damage. Autophagy. 2009;5:61–74. doi: 10.4161/auto.5.1.7272. [PubMed] [Cross Ref]
228. Huang Q, Wu YT, Tan HL, Ong CN, Shen H-M. A novel function of poly(ADP-ribose) polymerase-1 in modulation of autophagy and necrosis under oxidative stress. Cell Death Differ. 2009;16:264–277. doi: 10.1038/cdd.2008.151. [PubMed] [Cross Ref]
229. He C, Klionsky DJ. Atg9 trafficking in autophagy-related pathways. Autophagy. 2007;3:271–274. [PubMed]
230. Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001;20:5971–5981. doi: 10.1093/emboj/20.21.5971. [PubMed] [Cross Ref]
231. Böck BC, Tagscherer KE, Fassl A, Kramer A, Oehme I, Zentgraf HW, et al. The PEA-15 protein regulates autophagy via activation of JNK. J Biol Chem. 2010;285:21644–21654. doi: 10.1074/jbc.M109.096628. [PMC free article] [PubMed] [Cross Ref]
232. Leu JI-J, Pimkina J, Frank A, Murphy ME, George DL. A small molecule inhibitor of inducible heat shock protein 70. Mol Cell. 2009;36:15–27. doi: 10.1016/j.molcel.2009.09.023. [PMC free article] [PubMed] [Cross Ref]
233. Klionsky DJ. Protein transport from the cytoplasm into the vacuole. J Membr Biol. 1997;157:105–115. doi: 10.1007/s002329900220. [PubMed] [Cross Ref]
234. Seglen PO, Gordon PB, Holen I. Non-selective autophagy. Semin Cell Biol. 1990;1:441–448. [PubMed]
235. Krick R, Muehe Y, Prick T, Bremer S, Schlotterhose P, Eskelinen E-L, et al. Piecemeal microautophagy of the nucleus requires the core macroautophagy genes. Mol Biol Cell. 2008;19:4492–4505. doi: 10.1091/mbc.E08-04-0363. [PMC free article] [PubMed] [Cross Ref]
236. Roberts P, Moshitch-Moshkovitz S, Kvam E, O'Toole E, Winey M, Goldfarb DS. Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae. Mol Biol Cell. 2003;14:129–141. doi: 10.1091/mbc.E02-08-0483. [PMC free article] [PubMed] [Cross Ref]
237. Chu CT. A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum Mol Genet. 2010;19:28–37. doi: 10.1093/hmg/ddq143. [PMC free article] [PubMed] [Cross Ref]
238. Dagda RK, Cherra SJ, III, Kulich SM, Tandon A, Park D, Chu CT. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009;284:13843–13855. doi: 10.1074/jbc.M808515200. [PMC free article] [PubMed] [Cross Ref]
239. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 2010;107:378–383. doi: 10.1073/pnas.0911187107. [PubMed] [Cross Ref]
240. Budovskaya YV, Stephan JS, Reggiori F, Klionsky DJ, Herman PK. The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. J Biol Chem. 2004;279:20663–20671. doi: 10.1074/jbc.M400272200. [PMC free article] [PubMed] [Cross Ref]
241. Shahab S, Namolovan A, Mogridge J, Kim PK, Brumell JH. Bacterial toxins can inhibit host cell autophagy through cAMP generation. Autophagy. 2011;7:957–965. [PubMed]
242. Shahnazari S, Yen WL, Birmingham CL, Shiu J, Namolovan A, Zheng YT, et al. A diacylglyceroldependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host Microbe. 2010;8:137–146. doi: 10.1016/j.chom.2010.07.002. [PubMed] [Cross Ref]
243. Tallóczy Z, Virgin HW, IV, Levine B. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy. 2006;2:24–29. [PubMed]
244. Yano T, Mita S, Ohmori H, Oshima Y, Fujimoto Y, Ueda R, et al. Autophagic control of listeria through intracellular innate immune recognition in drosophila. Nat Immunol. 2008;9:908–916. doi: 10.1038/ni.1634. [PMC free article] [PubMed] [Cross Ref]
245. Nazarko VY, Nazarko TY, Farre JC, Stasyk OV, Warnecke D, Ulaszewski S, et al. Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus formation in Pichia pastoris. Autophagy. 2011;7:375–385. [PMC free article] [PubMed]
246. Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 2010;141:1146–1158. doi: 10.1016/j.cell.2010.05.008. [PubMed] [Cross Ref]
247. Neely KM, Green KN, Laferla FM. Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a γ-secretase-independent manner. J Neurosci. 2011;31:2781–2791. doi: 10.1523/JNEUROSCI.5156-10.2010. [PMC free article] [PubMed] [Cross Ref]
248. Martin KR, Xu Y, Looyenga BD, Davis RJ, Wu CL, Tremblay ML, et al. Identification of PTPs as an autophagic phosphatase. J Cell Sci. 2011;124:812–819. doi: 10.1242/jcs.080341. [PubMed] [Cross Ref]
249. Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009;10:513–525. doi: 10.1038/nrm2728. [PubMed] [Cross Ref]
250. Gutierrez MG, Munafo DB, Beron W, Colombo MI. Rab7 is required for the normal progression of the autophagic pathway in mammalian cells. J Cell Sci. 2004;117:2687–2697. doi: 10.1242/jcs.01114. [PubMed] [Cross Ref]
251. Jäger S, Bucci C, Tanida I, Ueno T, Kominami E, Saftig P, et al. Role for Rab7 in maturation of late autophagic vacuoles. J Cell Sci. 2004;117:4837–4848. doi: 10.1242/jcs.01370. [PubMed] [Cross Ref]
252. Munafó DB, Colombo MI. Induction of autophagy causes dramatic changes in the subcellular distribution of GFP-Rab24. Traffic. 2002;3:472–482. doi: 10.1034/j.1600-0854.2002.30704.x. [PubMed] [Cross Ref]
253. Hirota Y, Tanaka Y. A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions. Cell Mol Life Sci. 2009;66:2913–2932. doi: 10.1007/s00018-009-0080-9. [PubMed] [Cross Ref]
254. Itoh T, Fujita N, Kanno E, Yamamoto A, Yoshimori T, Fukuda M. Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation. Mol Biol Cell. 2008;19:2916–2925. doi: 10.1091/mbc.E07-12-1231. [PMC free article] [PubMed] [Cross Ref]
255. Itoh T, Kanno E, Uemura T, Waguri S, Fukuda M. OATL1, a novel autophagosome-resident Rab33BGAP, regulates autophagosomal maturation. J Cell Biol. 2011;192:839–853. doi: 10.1083/jcb.201008107. [PMC free article] [PubMed] [Cross Ref]
256. Kwon SI, Cho HJ, Jung JH, Yoshimoto K, Shirasu K, Park OK. The Rab GTPase RabG3b functions in autophagy and contributes to tracheary element differentiation in Arabidopsis. Plant J. 2010;64:151–164. [PubMed]
257. Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan K-L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008;10:935–945. doi: 10.1038/ncb1753. [PMC free article] [PubMed] [Cross Ref]
258. Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, et al. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010;17:666–676. doi: 10.1038/cdd.2009.149. [PMC free article] [PubMed] [Cross Ref]
259. Kang R, Tang D, Livesey KM, Schapiro N, Lotze MT, Zeh HJ. The receptor for advanced glycation end-products (RAGE) protects pancreatic tumor cells against oxidative injury. Antioxid Redox Signal. 2011;15:2175–2184. doi: 10.1089/ars.2010.3378. [PMC free article] [PubMed] [Cross Ref]
260. Geng J, Nair U, Yasumura-Yorimitsu K, Klionsky DJ. Post-Golgi Sec proteins are required for autophagy in Saccharomyces cerevisiae. Mol Biol Cell. 2010;21:2257–2269. doi: 10.1091/mbc.E09-11-0969. [PMC free article] [PubMed] [Cross Ref]
261. Jiang H, Martin V, Gomez-Manzano C, Johnson DG, Alonso M, White E, et al. The RB-E2F1 pathway regulates autophagy. Cancer Res. 2010;70:7882–7893. doi: 10.1158/0008-5472.CAN-10-1604. [PMC free article] [PubMed] [Cross Ref]
262. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007;26:1749–1760. doi: 10.1038/sj.emboj.7601623. [PubMed] [Cross Ref]
263. Punnonen E-L, Reunanen H, Hirsimaki P, Lounatmaa K. Filipin labelling and intramembrane particles on the membranes of early and later autophagic vacuoles in Ehrlich ascites cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;54:317–326. doi: 10.1007/BF02899229. [PubMed] [Cross Ref]
264. Opipari AW, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR. Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res. 2004;64:696–703. doi: 10.1158/0008-5472.CAN-03-2404. [PubMed] [Cross Ref]
265. Klionsky DJ, Cuervo AM, Dunn WA, Jr, Levine B, van der Klei I, Seglen PO. How shall I eat thee? Autophagy. 2007;3:413–416. [PubMed]
266. Scott RC, Schuldiner O, Neufeld TP. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004;7:167–178. doi: 10.1016/j.devcel.2004.07.009. [PubMed] [Cross Ref]
267. Kraft C, Deplazes A, Sohrmann M, Peter M. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol. 2008;10:602–610. doi: 10.1038/ncb1723. [PubMed] [Cross Ref]
268. Yorimitsu T, Zaman S, Broach JR, Klionsky DJ. Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae. Mol Biol Cell. 2007;18:4180–4189. doi: 10.1091/mbc.E07-05-0485. [PMC free article] [PubMed] [Cross Ref]
269. Hillwig MS, Contento AL, Meyer A, Ebany D, Bassham DC, Macintosh GC. RNS2, a conserved member of the RNase T2 family, is necessary for ribosomal RNA decay in plants. Proc Natl Acad Sci USA. 2011;108:1093–1098. doi: 10.1073/pnas.1009809108. [PubMed] [Cross Ref]
270. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009;11:385–396. doi: 10.1038/ncb1846. [PubMed] [Cross Ref]
271. Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009;11:468–476. doi: 10.1038/ncb1854. [PMC free article] [PubMed] [Cross Ref]
272. Dokudovskaya S, Waharte F, Schlessinger A, Pieper U, Devos DP, Cristea IM, et al. A conserved coatomerrelated complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae. Mol Cell Proteomics. 2011;10:110.006478. [PMC free article] [PubMed]
273. Nair U, Jotwani A, Geng J, Gammoh N, Richerson D, Yen W-L, et al. SNARE proteins are required for macroautophagy. Cell. 2011;146:290–302. doi: 10.1016/j.cell.2011.06.022. [PMC free article] [PubMed] [Cross Ref]
274. Ishihara N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, Kihara A, et al. Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell. 2001;12:3690–3702. [PMC free article] [PubMed]
275. Zhang Y, Yan L, Zhou Z, Yang P, Tian E, Zhang K, et al. SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell. 2009;136:308–321. doi: 10.1016/j.cell.2008.12.022. [PubMed] [Cross Ref]
276. Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, Lelek M, et al. Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe. 2010;8:433–444. doi: 10.1016/j.chom.2010.10.009. [PubMed] [Cross Ref]
277. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105:3374–3379. doi: 10.1073/pnas.0712145105. [PubMed] [Cross Ref]
278. Birmingham CL, Canadien V, Kaniuk NA, Steinberg BE, Higgins DE, Brumell JH. Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature. 2008;451:350–354. doi: 10.1038/nature06479. [PubMed] [Cross Ref]
279. Bhardwaj V, Kanagawa O, Swanson PE, Unanue ER. Chronic Listeria infection in SCID mice: requirements for the carrier state and the dual role of T cells in transferring protection or suppression. J Immunol. 1998;160:376–384. [PubMed]
280. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136:521–534. doi: 10.1016/j.cell.2008.11.044. [PubMed] [Cross Ref]
281. Deretic V. Autophagy in immunity and cell-autonomous defense against intracellular microbes. Immunol Rev. 2011;240:92–104. doi: 10.1111/j.1600-065X.2010.00995.x. [PMC free article] [PubMed] [Cross Ref]
282. Reef S, Zalckvar E, Shifman O, Bialik S, Sabanay H, Oren M, et al. A short mitochondrial form of p19ARF induces autophagy and caspase-independent cell death. Mol Cell. 2006;22:463–475. doi: 10.1016/j.molcel.2006.04.014. [PubMed] [Cross Ref]
283. Cai Q, Lu L, Tian J-H, Zhu Y-B, Qiao H, Sheng Z-H. Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons. Neuron. 2010;68:73–86. doi: 10.1016/j.neuron.2010.09.022. [PMC free article] [PubMed] [Cross Ref]
284. Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11:1305–1314. doi: 10.1038/ncb1975. [PubMed] [Cross Ref]
285. Ghidoni R, Houri JJ, Giuliani A, Ogier-Denis E, Parolari E, Botti S, et al. The metabolism of sphingo(glyco)lipids is correlated with the differentiation-dependent autophagic pathway in HT-29 cells. Eur J Biochem. 1996;237:454–459. doi: 10.1111/j.1432-033.1996.0454k.x. [PubMed] [Cross Ref]
286. Lavieu G, Scarlatti F, Sala G, Levade T, Ghidoni R, Botti J, et al. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision? Autophagy. 2007;3:45–47. [PubMed]
287. Rong Y, McPhee C, Deng S, Huang L, Chen L, Liu M, et al. Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proc Natl Acad Sci USA. 2011;108:7826–7831. doi: 10.1073/pnas.1013800108. [PubMed] [Cross Ref]
288. Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, Chen GC. Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. EMBO J. 2011;30:636–651. doi: 10.1038/emboj.2010.338. [PubMed] [Cross Ref]
289. Renna M, Schaffner C, Winslow AR, Menzies FM, Peden AA, Floto RA, et al. Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. J Cell Sci. 2011;124:469–482. doi: 10.1242/jcs.076489. [PubMed] [Cross Ref]
290. Herrero-Martín G, Hoyer-Hansen M, Garcia-Garcia C, Fumarola C, Farkas T, Lopez-Rivas A, et al. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J. 2009;28:677–685. doi: 10.1038/emboj.2009.8. [PubMed] [Cross Ref]
291. Shintani T, Huang W-P, Stromhaug PE, Klionsky DJ. Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev Cell. 2002;3:825–837. doi: 10.1016/S1534-5807(02)00373-8. [PMC free article] [PubMed] [Cross Ref]
292. Narita M, Young AR, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, et al. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science. 2011;332:966–970. doi: 10.1126/science.1205407. [PMC free article] [PubMed] [Cross Ref]
293. Ogawa M, Yoshikawa Y, Kobayashi T, Mimuro H, Fukumatsu M, Kiga K, et al. A tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe. 2011;9:376–389. doi: 10.1016/j.chom.2011.04.010. [PubMed] [Cross Ref]
294. Settembre C, Di Malta C, Polito VA, Arencibia MG, Vetrini F, Erdin S, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332:1429–1433. doi: 10.1126/science.1204592. [PubMed] [Cross Ref]
295. Bensaad K, Cheung EC, Vousden KH. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J. 2009;28:3015–3026. doi: 10.1038/emboj.2009.242. [PMC free article] [PubMed] [Cross Ref]
296. Abeliovich H, Darsow T, Emr SD. Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARESec1p complex composed of Tlg2p and Vps45p. EMBO J. 1999;18:6005–6016. doi: 10.1093/emboj/18.21.6005. [PubMed] [Cross Ref]
297. He P, Peng Z, Luo Y, Wang L, Yu P, Deng W, et al. High-throughput functional screening for autophagy-related genes and identification of TM9SF1 as an autophagosome-inducing gene. Autophagy. 2009;5:52–60. doi: 10.4161/auto.5.1.7247. [PubMed] [Cross Ref]
298. Yu C, Wang L, Lv B, Lu Y, Zeng L, Chen Y, et al. TMEM74, a lysosome and autophagosome protein, regulates autophagy. Biochem Biophys Res Commun. 2008;369:622–629. doi: 10.1016/j.bbrc.2008.02.055. [PubMed] [Cross Ref]
299. Wang L, Yu C, Lu Y, He P, Guo J, Zhang C, et al. TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis. Apoptosis. 2007;12:1489–1502. doi: 10.1007/s10495-007-0073-9. [PubMed] [Cross Ref]
300. Jacinto E. What controls TOR? IUBMB Life. 2008;60:483–496. doi: 10.1002/iub.56. [PubMed] [Cross Ref]
301. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009;137:873–886. doi: 10.1016/j.cell.2009.03.046. [PMC free article] [PubMed] [Cross Ref]
302. Pearce LR, Huang X, Boudeau J, Pawlowski R, Wullschleger S, Deak M, et al. Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J. 2007;405:513–522. doi: 10.1042/BJ20070540. [PubMed] [Cross Ref]
303. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009;284:8023–8032. doi: 10.1074/jbc.M900301200. [PMC free article] [PubMed] [Cross Ref]
304. N'Guessan P, Pouyet L, Gosset G, Hamlaoui S, Seillier M, Cano C, et al. Absence of tumor suppressor Tumor Protein 53-Induced Nuclear Protein 1 sensitizes mouse thymocytes and embryonic fibroblasts to redox-driven apoptosis. Antioxid Redox Signal. 2011;15:1639–1653. doi: 10.1089/ars.2010.3553. [PubMed] [Cross Ref]
305. Nowak J, Archange C, Tardivel-Lacombe J, Pontarotti P, Pebusque MJ, Vaccaro MI, et al. The TP53INP2 protein is required for autophagy in mammalian cells. Mol Biol Cell. 2009;20:870–881. doi: 10.1091/mbc.E08-07-0671. [PMC free article] [PubMed] [Cross Ref]
306. Lynch-Day MA, Bhandari D, Menon S, Huang J, Cai H, Bartholomew CR, et al. Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy. Proc Natl Acad Sci USA. 2010;107:7811–7816. doi: 10.1073/pnas.1000063107. [PubMed] [Cross Ref]
307. N'Diaye EN, Kajihara KK, Hsieh I, Morisaki H, Debnath J, Brown EJ. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep. 2009;10:173–179. doi: 10.1038/embor.2008.238. [PubMed] [Cross Ref]
308. Chan EYW, Kir S, Tooze SA. siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy. J Biol Chem. 2007;282:25464–25474. doi: 10.1074/jbc.M703663200. [PubMed] [Cross Ref]
309. Young ARJ, Chan EYW, Hu XW, Köchl R, Crawshaw SG, High S, et al. Starvation and ULK1dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006;119:3888–3900. doi: 10.1242/jcs.03172. [PubMed] [Cross Ref]
310. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol. 2010;22:132–139. doi: 10.1016/ [PubMed] [Cross Ref]
311. Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH, et al. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol. 2006;8:688–699. doi: 10.1038/ncb1426. [PubMed] [Cross Ref]
312. Hoffman M, Chiang H-L. Isolation of degradation-deficient mutants defective in the targeting of fructose-1,6-bisphosphatase into the vacuole for degradation in Saccharomyces cerevisiae. Genetics. 1996;143:1555–1566. [PubMed]
313. Darsow T, Rieder SE, Emr SD. A multispecificity syntaxin homolog, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol. 1997;138:517–529. doi: 10.1083/jcb.138.3.517. [PMC free article] [PubMed] [Cross Ref]
314. Fader CM, Sanchez DG, Mestre MB, Colombo MI. TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta. 2009;1793:1901–1916. [PubMed]
315. Moreau K, Ravikumar B, Renna M, Puri C, Rubinsztein DC. Autophagosome precursor maturation requires homotypic fusion. Cell. 2011;146:303–317. doi: 10.1016/j.cell.2011.06.023. [PMC free article] [PubMed] [Cross Ref]
316. Furuta N, Fujita N, Noda T, Yoshimori T, Amano A. Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell. 2010;21:1001–1010. doi: 10.1091/mbc.E09-08-0693. [PMC free article] [PubMed] [Cross Ref]
317. Tresse E, Salomons FA, Vesa J, Bott LC, Kimonis V, Yao TP, et al. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy. 2010;6:217–227. doi: 10.4161/auto.6.2.11014. [PMC free article] [PubMed] [Cross Ref]
318. Ju JS, Fuentealba RA, Miller SE, Jackson E, Piwnica-Worms D, Baloh RH, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009;187:875–888. doi: 10.1083/jcb.200908115. [PMC free article] [PubMed] [Cross Ref]
319. Donohue E, Tovey A, Vogl AW, Arns S, Sternberg E, Young RN, et al. Inhibition of autophagosome formation by the benzoporphyrin derivative verteporfin. J Biol Chem. 2011;286:7290–7300. doi: 10.1074/jbc.M110.139915. [PMC free article] [PubMed] [Cross Ref]
320. Vaccaro MI, Ropolo A, Grasso D, Iovanna JL. A novel mammalian trans-membrane protein reveals an alternative initiation pathway for autophagy. Autophagy. 2008;4:388–390. [PubMed]
321. Ropolo A, Grasso D, Pardo R, Sacchetti ML, Archange C, Lo Re A, et al. The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells. J Biol Chem. 2007;282:37124–37133. doi: 10.1074/jbc.M706956200. [PubMed] [Cross Ref]
322. Oku M, Nishimura T, Hattori T, Ano Y, Yamashita S, Sakai Y. Role of Vac8 in formation of the vacuolar sequestering membrane during micropexophagy. Autophagy. 2006;2:272–279. [PubMed]
323. Furuta N, Fujita N, Noda T, Yoshimori T, Amano A. Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell. 2010;21:1001–1010. doi: 10.1091/mbc.E09-08-0693. [PMC free article] [PubMed] [Cross Ref]
324. Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A. WIPI-1α (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene. 2004;23:9314–9325. doi: 10.1038/sj.onc.1208331. [PubMed] [Cross Ref]
325. Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbé S, Clague MJ, et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6:506–522. doi: 10.4161/auto.6.4.11863. [PubMed] [Cross Ref]
326. Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, et al. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008;13:1211–1218. doi: 10.1111/j.1365-2443.2008.01238.x. [PubMed] [Cross Ref]
327. Nyfeler B, Bergman P, Triantafellow E, Wilson CJ, Zhu Y, Radetich B, et al. Relieving autophagy and 4EBP1 from rapamycin resistance. Mol Cell Biol. 2011;31:2867–2876. doi: 10.1128/MCB.05430-11. [PMC free article] [PubMed] [Cross Ref]
328. Kaser A, Blumberg RS. Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease. Semin Immunol. 2009;21:156–163. doi: 10.1016/j.smim.2009.01.001. [PubMed] [Cross Ref]
329. Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell. 2005;120:159–162. doi: 10.1016/S0092-8674(05)00043-7. [PubMed] [Cross Ref]
330. Criollo A, Maiuri MC, Tasdemir E, Vitale I, Fiebig AA, Andrews D, et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007;14:1029–1039. [PubMed]
331. Kweon Y, Rothe A, Conibear E, Stevens TH. Ykt6p is a multifunctional yeast R-SNARE that is required for multiple membrane transport pathways to the vacuole. Mol Biol Cell. 2003;14:1868–1881. doi: 10.1091/mbc.E02-10-0687. [PMC free article] [PubMed] [Cross Ref]
332. Huang J, Birmingham CL, Shahnazari S, Shiu J, Zheng YT, Smith AC, et al. Antibacterial autophagy occurs at PI(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase. Autophagy. 2011;7:17–26. doi: 10.4161/auto.7.1.13840. [PMC free article] [PubMed] [Cross Ref]
333. Zoppino FC, Militello RD, Slavin I, Alvarez C, Colombo MI. Autophagosome formation depends on the small GTPase Rab1 and functional ER exit sites. Traffic. 2010;11:1246–1261. doi: 10.1111/j.1600-0854.2010.01086.x. [PubMed] [Cross Ref]
334. Tang H-W, Wang Y-B, Wang S-L, Wu M-H, Lin S-Y, Chen G-C. Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. EMBO J. 2011;30:2867–2876. doi: 10.1038/emboj.2010.338. [PubMed] [Cross Ref]
335. Grasso D, Ropolo A, Lo Re A, Boggio V, Molejon MI, Iovanna JL, et al. Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. J Biol Chem. 2011;286:8308–8324. doi: 10.1074/jbc.M110.197301. [PMC free article] [PubMed] [Cross Ref]

Articles from Autophagy are provided here courtesy of Taylor & Francis