Fig. 1.

Simplified autophagy signaling pathway and regulation. a Nutrition deprivation inhibits mTOR, which in turn activates ULK1 complex. Energy deprivation is sensed by AMPK to suppress mTOR and activates ULK1 complex. Activated ULK1 complex recruits Vps34-Beclin-1 complex to produce PI3P and initiates phagosome formation. b Two conjugation systems, Atg12–Atg5-Atg16L and LC3–PE, facilitate phagophore membrane elongation and autophagosome maturation. c NAD-dependent deacetylase Sirt1 catalyzes deacetylation of Vps34, Beclin1, Atg5, Atg7, and LC3 to promote autophagy. d Transcription factors TFEB and FoxO translocate to the nuclear to induce autophagy-related gene expression. Their transcription activity can be inhibited by phosphorylation caused by mTOR or AKT, respectively. Phosphorylated TFEB is digested by proteasome; ZKSCAN3 repress autophagy-related gene transcription.