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1.  Trs85 is Required for Macroautophagy, Pexophagy and Cytoplasm to Vacuole Targeting in Yarrowia lipolytica and Saccharomyces cerevisiae 
Autophagy  2005;1(1):37-45.
Yarrowia lipolytica was recently introduced as a new model organism to study peroxisome degradation in yeasts. Transfer of Y. lipolytica cells from oleate/ethylamine to glucose/ammonium chloride medium leads to selective macroautophagy of peroxisomes. To decipher the molecular mechanisms of macropexophagy we isolated mutants of Y. lipolytica defective in the inactivation of peroxisomal enzymes under pexophagy conditions. Through this analysis we identified the gene YlTRS85, the ortholog of Saccharomyces cerevisiae TRS85 that encodes the 85 kDa subunit of transport protein particle (TRAPP). A parallel genetic screen in S. cerevisiae also identified the trs85 mutant. Here, we report that Trs85 is required for nonspecific autophagy, pexophagy and the cytoplasm to vacuole targeting pathway in both yeasts.
PMCID: PMC1828867  PMID: 16874038
autophagy; TRAPP; early secretory pathway; protein targeting; vacuole; yeast
2.  Atg9 Cycles between Mitochondria and the Pre-Autophagosomal Structure in Yeasts 
Autophagy  2005;1(2):101-109.
Autophagy is a degradative process conserved among eukaryotic cells. It allows the elimination of cytoplasm including aberrant protein aggregates and damaged organelles. Accordingly, it is implicated in normal developmental processes and also serves a protective role in tumor suppression and elimination of invading pathogens, whereas defects in autophagy are associated with various human diseases including cancer and neurodegeneration. Atg proteins mediate the sequestration event that occurs at the preautophagosomal structure (PAS) by catalyzing the formation of double-membrane vesicles, termed autophagosomes. In Saccharomyces cerevisiae, the integral membrane protein Atg9 that is required for autophagy cycles through the PAS. Here, we demonstrate that Atg9 shuttles between this location and mitochondria. These data support a new model where mitochondria may provide at least part of the autophagosomal lipids and suggest a novel cellular function for this well-studied organelle.
PMCID: PMC1762033  PMID: 16874040
autophagy; cytoplasm to vacuole targeting; endoplasmic reticulum; lysosome
3.  Autophagy and Inflammatory Cell Death, Partners of Innate Immunity 
Autophagy  2005;1(3):174-176.
By law in the evolutionary jungle, any host defense mechanism that efficiently kills microbes also exerts a strong selective pressure for tolerant variants to emerge. As a consequence, pathogens can be exploited as powerful tools to examine host defense mechanisms. Recent studies of the confrontation between macrophages and the opportunistic pathogen Legionella pneumophila have revealed a regulatory mechanism that may link autophagy to pyroptosis, a type of programmed cell death. Building from the extensive literature on autophagy, cell death, and innate immunity, we propose here a testable model in which the NOD-LRR protein Naip5 dictates whether murine macrophages elevate autophagy or pyroptosis as a barrier to infection.
PMCID: PMC1584281  PMID: 16874072
4.  Macrophages Rapidly Transfer Pathogens from Lipid Raft Vacuoles to Autophagosomes 
Autophagy  2005;1(1):53-58.
Macrophages activate autophagy as an immediate response to Legionella pneumophila infection, but what marks the pathogen phagosome as a target for the autophagy machinery is not known. Because a variety of bacteria, parasites, viruses, and toxins that associate with the endoplasmic reticulum enter host cells by a cholesterol-dependent route, we tested the hypothesis that autophagy is triggered when microbes engage components of lipid raft domains. As the intracellular respiratory pathogen L. pneumophila or the extracellular uropathogen FimH+ Escherichia coli entered macrophages by a cholesterol-sensitive mechanism, they immediatezly resided in vacuoles rich in glycosylphosphatidylinositol moieties and the autophagy enzyme Atg7. As expected for autophagosomes, the vacuoles sequentially acquired the endoplasmic reticulum protein BiP, the autophagy markers Atg8 and monodansyl-cadaverine, and the lysosomal protein LAMP-1. A robust macrophage response to the pathogens was cholesterol-dependent, since fewer Atg7-rich vacuoles were observed when macrophages were pretreated with methyl-╬▓-cyclodextrin or filipin. A model in which macrophages exploit autophagy to capture pathogens within the lipid raft pathway for antigen presentation prior to disposal in lysosomes is discussed.
PMCID: PMC1584280  PMID: 16874021
Legionella pneumophila; uropathogenic E. coli; cholesterol; endoplasmic reticulum; lysosomes

Results 1-4 (4)