Role and regulation of starvation-induced autophagy in the Drosophila fat body.
In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including ATG1 and ATG5, does not restore growth to TOR mutant cells. Instead, inhibition of autophagy enhances TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor.
Scott
Ryan C
RC
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455 USA.
Schuldiner
Oren
O
Neufeld
Thomas P
TP
D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002455:Cell Division; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster; D005216:Fat Body / Q000502:physiology*; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental; D008247:Lysosomes / Q000378:metabolism; D008854:Microscopy, Electron; D008954:Models, Biological; D010587:Phagocytosis; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D000071183:Autophagy-Related Proteins; D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D029701:Saccharomyces cerevisiae Proteins; D058570:TOR Serine-Threonine Kinases; C477823:ATG1 protein, S cerevisiae; C416303:target of rapamycin protein, Drosophila