In our system, overexpression of Sec61α was sufficient to suppress starvation-induced autophagy.
In conclusion, PDGF-BB signaling through mTORC2 is important for the ability of PDGF-BB to suppress starvation-induced cleavage of caspase 3, but not for chemotaxis.
This is consistent with observations in the Drosophila fat body, whereby signaling through TOR and PI3K is necessary and sufficient to suppress starvation-induced autophagy and yet S6K promotes autophagy [ 65].
These anti-apoptotic Bcl-2 proteins suppress starvation-induced autophagy by inhibiting the formation of the complex between Beclin1 and the class III phosphatidylinositol 3-kinase (PI3K) Vps34 [28].
Consistent with a critical role for mTORC2 in Akt activation, we found that in Rictor-deficient cells, which are blunted in their ability to activate Akt, PDGF-BB was not able to suppress starvation-induced caspase-3 cleavage, whereas it did so in control cells.
Conversely, overexpression of ectopic Sec61α suppressed starvation-induced LysoTracker staining (Fig. 5H), and resulted in fewer and smaller mCherry-Atg8a-containing autophagosomes (Fig. 5I).
Tor suppresses starvation-induced autophagy in the Drosophila fat body [56] and yeast Tor controls autophagy by responding to nutrient availability [32].
A recent study found that dietary leucine specifically rescues starvation-induced death in gpb-2 mutants, and that dietary leucine suppresses starvation-induced stress and lifespan extension in wild-type worms [38], demonstrating the importance of this amino acid in regulating dietary responses in C. elegans.
Lower pH not only decreases basal autophagy, but also suppresses starvation-induced autophagy, which in turn sensitizes to cell death.
Overexpression of Atg1 strongly promotes autophagy in Drosopohila, while expression of a kinase dead form suppresses starvation-induced autophagy [ 10].
Ectopic PI3K signaling overrides loss of a positive nutrient signal and suppresses starvation-induced autophagy [ 22, 43].
