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1.  Inhibiting autophagy by shRNA knockdown 
Autophagy  2013;9(10):1449-1450.
A glance through Autophagy or any other journal in this field shows that it is very common to block autophagy by RNA interference-based knockdown of ATG mRNAs in mammalian cell lines. Our lab’s experience is that this approach can easily make for failed experiments because good knockdown of even essential autophagy regulators does not necessarily mean you will get good inhibition of autophagy, and, over time, cells can find ways to circumvent the inhibitory effects of the knockdown.
doi:10.4161/auto.24895
PMCID: PMC3974882  PMID: 23800703
autophagy; shRNA; ATG5; knockdown; RNA interference
2.  The intense gravitational attraction of autophagy 
Autophagy  2013;9(8):1127-1128.
In the course of my work as Autophagy editor, I try to gauge the overall patterns of interest in autophagy research. Not surprisingly, the number of papers associated with this topic has increased steadily. However, that trend provides only one glimpse into the way interest in this field has been changing—that the number of people working on autophagy has expanded. Perhaps not surprisingly, the number of different research areas that now include autophagy studies is also increasing. Thus, I decided to carry out an informal, imprecise analysis of the number of different journals (presumably reflecting in part the number of topics) that include papers on autophagy.
doi:10.4161/auto.25572
PMCID: PMC3748185
autophagy; black hole; gravity; lysosome; stress; vacuole
3.  Autophagy and gene therapy combine in the treatment of liver disease 
Autophagy  2013;9(7):945-946.
Molecular biology holds the promise not only of increasing our understanding of basic cell biology, but also of advancing our ability to design targeted therapeutic methods for treating a range of diseases. One example that seems to hold tremendous potential is gene therapy, the use of exogenous DNA to replace or suppress a mutant gene in the patient’s genome, or to boost the activity of a normal gene. A recent report (highlighted in a punctum in this issue of the journal) has brought autophagy into the gene therapy realm.
doi:10.4161/auto.24475
PMCID: PMC3722329  PMID: 23590992
TFEB; lysosome; macroautophagy; α1-antitrypsin deficiency
4.  A unique hairpin-type tail-anchored SNARE starts to solve a long-time puzzle 
Autophagy  2013;9(6):813-814.
Macroautophagy mediates recycling of intracellular material by a multistep pathway, ultimately leading to the fusion of closed double-membrane structures, called autophagosomes, with the lysosome. This event ensures the degradation of the autophagosome content by lysosomal proteases followed by the release of macromolecules by permeases and, thus, it accomplishes the purpose of macroautophagy (hereafter referred to as autophagy). Because fusion of unclosed autophagosomes (i.e., phagophores) with the lysosome would fail to degrade the autophagic cargo, this critical step has to be tightly controlled. Yet, until recently, little was known about the regulation of this event and the factors orchestrating it. A punctum in this issue highlights the recent paper by Noboru Mizushima and his collaborators that answered the question of how premature fusion of phagophores with the lysosome is prevented prior to completion of autophagosome closure.
doi:10.4161/auto.24359
PMCID: PMC3672291  PMID: 23575358
autophagosome; fusion; glycine zipper; lysosome; SNARE
5.  The many uses of autophagosomes 
Autophagy  2013;9(5):633-634.
Autophagy has emerged as a significant innate immune response to pathogens. Typically, autophagosomes deliver their contents to lysosomes for degradation. Some pathogens such as Salmonella enterica serovar Typhimurium succumb to autophagy and are transported to lysosomes for degradation. Yet, many professional pathogens, including Legionella pneumophila and Burkholderia cenocepacia, subvert this pathway exploiting autophagy to their advantage.
doi:10.4161/auto.24146
PMCID: PMC3669174  PMID: 23507956
autophagosomes; bacteria; lysosome fusion; Anaplasma; Legionella; Burkholderia; Francisella
6.  Ancient autophagy 
Autophagy  2013;9(4):445-446.
These days, when we talk about the origin of a protein, or even a pathway, we are typically referring to evolutionary lineages based on nucleotide sequences. For example, is a particular protein’s function conserved? How far back did it first appear? Are there homologs in higher eukaryotes? However, a simpler question (or perhaps I should say, a non-molecular biology question) is when was the process first detected in the paleontological record? Of course I assumed that macroautophagy was ancient, but a new finding (see p. 632 in this issue of the journal) provides an unexpected—and exciting—piece of information for our field. For the first time, scientists have discovered fossil evidence for an actual subcellular pathway—and it looks like it might actually be autophagy (I admit I am biased, but you can decide for yourself).
doi:10.4161/auto.23907
PMCID: PMC3627661  PMID: 23388466
autophagy; fossil; lysosome; stress; vacuole
7.  Finding autophagy 
Autophagy  2013;9(3):267.
To tell the truth, I find it difficult to work when flying, or even when sitting in an airport for an extended period of time. So, typically I take along a book to read. And when I truly cannot concentrate, for example when a flight is considerably delayed, I have even been known to resort to word puzzles. Depending on the type, they do not require much attention (that is, you can pick up right where you left off after you glance at the flight status screen for the twentieth or so time, even though you know nothing has changed), or effort (although you need to use a pen or pencil, not a keyboard), but nonetheless they can keep your mind somewhat occupied. I even rationalize doing them based on the assumption that they are sharpening my observational/pattern-finding skills. One type of word puzzle that is particularly mindless, but for that very reason I still enjoy in the above circumstances, is a word search; you are given a grid with letters and/or numbers, and a list of “hidden” terms, and you circle them within the grid, crossing them off the list as you go along. I do admit that the categories of terms used in the typical word searches can become rather mundane (breeds of dog, types of food, words that are followed by “stone,” words associated with a famous movie star, words from a particular television show, etc.). Therefore, on one of my last seminar trips I decided to generate my own word search, using the category of autophagy.
doi:10.4161/auto.23483
PMCID: PMC3590247  PMID: 23322216
autophagy; lysosome; stress; vacuole; word search
8.  Why just eat in, when you can also eat out? 
Autophagy  2013;9(2):119.
The current working definition of autophagy is the following: all processes in which intracellular material is degraded within the lysosome/vacuole and where the macromolecular constituents are recycled. There are several ways to classify the different types of autophagy. For example, we can separate autophagy into two primary types, based on the initial site of cargo sequestration. In particular, during microautophagy and chaperone-mediated autophagy, uptake occurs directly at the limiting membrane of the lysosome or vacuole. In contrast, macroautophagy—whether selective or nonselective—and endosomal microautophagy involve sequestration within an autophagosome or an omegasome, or late endosomes/multivesicular bodies, respectively; the key point being that in these types of autophagy the initial sequestration event does not occur at the limiting membrane of the degradative organelle. In any case, the cargo is ultimately delivered into the lysosome or vacuole lumen for subsequent degradation. Thus, I think most autophagy researchers view the degradative organelle as the ultimate destination of the pathway. Indeed, this fits with the general concept that organelles allow reactions to be compartmentalized. With regard to the lysosome or vacuole, this also confers a level of safety by keeping the lytic contents away from the remainder of the cell. If we are willing to slightly modify our definition of autophagy, with a focus on “degradation of a cell’s own components through the lysosomal/vacuolar machinery,” we can include a newly documented process, programmed nuclear destruction (PND).
doi:10.4161/auto.22915
PMCID: PMC3552876  PMID: 23159909
autophagy; lysosome; meiosis; spore; stress; vacuole
9.  Infographic 
Autophagy  2012;8(12):1707.
doi:10.4161/auto.22883
PMCID: PMC3541281
10.  Look people, “Atg” is an abbreviation for “autophagy-related.” That’s it. 
Autophagy  2012;8(9):1281-1282.
doi:10.4161/auto.21812
PMCID: PMC3442874  PMID: 22889836
autophagosome; lysosome; phagophore; stress; vacuole
11.  The autophagy community 
Autophagy  2012;8(7):1003.
There are various definitions of community. A definition that I found in one of my dictionaries is the following: “A social, religious, occupational, or other group sharing common characteristics or interests and perceived or perceiving itself as distinct in some respect from the larger society within which it exists.” Thus, I think it is fair to say that there is a worldwide autophagy community. That is, there is a group of researchers (our occupation), whose members share an interest in autophagy (our common characteristic), and that group is distinct from the larger society (I do not want to begin describing the many ways this applies). But do we feel like a community, and do we need a community? I suggest that a community is indeed beneficial, and I propose one mechanism for enhancing the development of the autophagy community.
doi:10.4161/auto.20666
PMCID: PMC3429537  PMID: 22647354
lysosome; methods; people; stress; vacuole
12.  Highlights from this issue 
Autophagy  2012;8(7):1004-1005.
doi:10.4161/auto.21310
PMCID: PMC3429538
13.  Autophagic cell death exists 
Autophagy  2012;8(6):867-869.
The term autophagic cell death (ACD) initially referred to cell death with greatly enhanced autophagy, but is increasingly used to imply a death-mediating role of autophagy, as shown by a protective effect of autophagy inhibition. In addition, many authors require that autophagic cell death must not involve apoptosis or necrosis. Adopting these new and restrictive criteria, and emphasizing their own failure to protect human osteosarcoma cells by autophagy inhibition, the authors of a recent Editor’s Corner article in this journal argued for the extreme rarity or nonexistence of autophagic cell death. We here maintain that, even with the more stringent recent criteria, autophagic cell death exists in several situations, some of which were ignored by the Editor’s Corner authors. We reject their additional criterion that the autophagy in ACD must be the agent of ultimate cell dismantlement. And we argue that rapidly dividing mammalian cells such as cancer cells are not the most likely situation for finding pure ACD.
doi:10.4161/auto.20380
PMCID: PMC3427251  PMID: 22652592
apoptosis; autophagy; autophagic cell death; cell death; necrosis
14.  Highlights from this issue 
Autophagy  2012;8(6):870-872.
doi:10.4161/auto.20876
PMCID: PMC3427252
15.  Autophagy contributes to lysosomal storage disorders 
Autophagy  2012;8(5):715-716.
Degradation in the lysosome/vacuole is not the final step of autophagy. In particular, for starvation-induced autophagy it is necessary to release the breakdown products back into the cytosol. However, some researchers ignore this last step and simply refer to the endpoint of autophagy as degradation, or perhaps even cargo delivery. In many cases this is not a serious issue; however, the analysis of autophagy’s role in certain diseases makes clear that this can be a significant error.
doi:10.4161/auto.19920
PMCID: PMC3625119  PMID: 22617443
autophagy; cholesterol; lipids; lysosome; stress
16.  Protocols, Toolboxes and Resource papers 
Autophagy  2012;8(3):291.
In the August 2009 issue of Autophagy, I indicated that we were launching a new category of article, Protocols. At that time, I noted that we would ultimately be placing these articles on a new site online. Well, that time has finally arrived (see www.landesbioscience.com/journals/autophagy/protocols/ for links to these papers). Therefore, it seems appropriate for me to briefly distinguish among three types of community-oriented papers, Protocol, Toolbox and Resource.
doi:10.4161/auto.19460
PMCID: PMC3337838  PMID: 22301999
autophagy; lysosome; methods; stress; vacuole
17.  SNARE Dance 
Autophagy  2012;8(3):294-296.
There is little doubt that humans rely on vision as their primary sensory input. However, various studies indicate that audiovisual combinations of data presentation actually enhance the ability of the learner to comprehend the information. We present an example of a musical-biological interface that provides an audible demonstration of SNARE protein function in the process of macroautophagy.
doi:10.4161/auto.19327
PMCID: PMC3337839  PMID: 22361578
protein targeting; SNARE protein; stress; vacuole; yeast
18.  Activation of autophagy is required for muscle homeostasis during physical exercise 
Autophagy  2011;7(12):1405-1406.
Skeletal muscle fibers of collagen VI null (Col6a1−/−) mice show signs of degeneration due to a block in autophagy, leading to the accumulation of damaged mitochondria and excessive apoptosis. Attempts to induce autophagic flux by subjecting these mutant mice to long-term or shorter bursts of physical activity are unsuccessful (see Grumati, et al., pp. 1415–23). In normal mice, the induction of autophagy in the skeletal muscles post-exercise is able to prevent the accumulation of damaged organelles and maintain cellular homeostasis. Thus, these studies provide an important connection between autophagy and exercise physiology.
doi:10.4161/auto.7.12.18315
PMCID: PMC3288013  PMID: 22082869
lysosome; metabolism; physiology; stress; vacuole
19.  Highlights from this issue 
Autophagy  2011;7(12):1407-1409.
doi:10.4161/auto.7.12.18505
PMCID: PMC3288014
20.  Impaired mitophagy at the heart of injury 
Autophagy  2011;7(12):1573-1574.
Recent publications link mitophagy mediated by PINK1 and Parkin with cardioprotection and attenuation of inflammation and cell death. The field is in need of methods to monitor mitochondrial turnover in vivo to support the development of new therapies targeting mitochondrial turnover.
doi:10.4161/auto.7.12.18175
PMCID: PMC3288037  PMID: 22082870
mitophagy; mitochondria; cardiac; ischemia; inflammation; Parkin; cytokine
21.  For the last time, it is GFP-Atg8, not Atg8-GFP (and the same goes for LC3) 
Autophagy  2011;7(10):1093-1094.
doi:10.4161/auto.7.10.15492
PMCID: PMC3625118  PMID: 21993240
Atg8; autophagosome; autophagy; lysosome; phagophore; stress; vacuole
22.  There is more to autophagy than induction 
Autophagy  2011;7(8):801-802.
Considerable attention has been paid to the topic of autophagy induction. In part, this is because of the potential for modulating this process for therapeutic purposes. Of course we know that induced autophagy can also be problematic—for example, when trying to eliminate an established tumor that might be relying on autophagy for its own cytoprotective uses. Accordingly, inhibitory mechanisms have been considered; however, the corresponding studies have tended to focus on the pathways that block autophagy under noninducing conditions, such as when nutrients are available. In contrast, relatively little is known about the mechanisms for inhibiting autophagy under inducing conditions. Yet, this type of regulation must be occurring on a routine basis. We know that dysregulation of autophagy, e.g., due to improper activation of Beclin 1 leading to excessive autophagy activity, can cause cell death.1 Accordingly, we assume that during starvation or other inducing conditions there must be a mechanism to modulate autophagy. That is, once you turn it on, you do not want to let it continue unchecked. But how is autophagy downregulated when the inducing conditions still exist?
doi:10.4161/auto.7.8.16609
PMCID: PMC3625120  PMID: 21636971
Atg1; autophagosome; flux; lysosome; macroautophagy; phagophore; regulation; stress; TOR; Ulk1; vacuole
23.  In the beginning there was babble… 
Autophagy  2012;8(8):1165-1167.
“Go to, let us go down, and there confound their language, that they may not understand one another's speech. …Therefore is the name of it called Babel; because the Lord did there confound the language of all the earth…”
Genesis 11:7,9
doi:10.4161/auto.20665
PMCID: PMC3625114  PMID: 22836666
Arabidopsis; autophagy; Caenorhabditis; genes; human; lysosome; mammalian; mouse; nomenclature; rat; stress; vacuole; Xenopus; yeast; zebrafish
24.  Vps34 is a phosphatidylinositol 3-kinase, not a phosphoinositide 3-kinase 
Autophagy  2011;7(6):563-564.
doi:10.4161/auto.7.6.14873
PMCID: PMC3625115  PMID: 21278489
autophagy; lipids; lysosome; phagophore; phosphatidylinositol; sequestration; stress; vacuole
25.  The autophagosome is overrated! 
Autophagy  2011;7(4):353-354.
doi:10.4161/auto.7.4.14730
PMCID: PMC3625117  PMID: 21258205
autophagy; lysosome; phagophore; sequestration; stress; vacuole

Results 1-25 (27)