[HTML][HTML] Role and regulation of starvation-induced autophagy in the Drosophila fat body

RC Scott, O Schuldiner, TP Neufeld - Developmental cell, 2004 - cell.com
RC Scott, O Schuldiner, TP Neufeld
Developmental cell, 2004cell.com
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 …
Abstract
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.
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