Fig. 2: Molecular mechanism of autophagy.
From: The role of sphingosine-1-phosphate in autophagy and related disorders
The process of autophagy at the molecular level involves five steps: initiation, nucleation, elongation and maturation, fusion, and degradation. The ULK1 complex (including ULK1, FIP200, ATG13, and ATG101) is the primary initiator of autophagy and can be regulated by mTOR and AMPK. The ULK1 complex activates the critical factor of nucleation, PI3KC3 complex (including Beclin1, ATG14L, Vps15, and Vps34), and recruits downstream proteins, such as WIPI proteins, ATG9-positive vesicles and ATG5-ATG12-ATG16L1 complex, for the elongation and maturation. LC3-I converts to LC3-II to facilitate autophagosome maturation. PI3K complex II, HOPS complex, RAB proteins, SNARE proteins, and the LC3 family proteins function in the fusion. Finally, the engulfed cargo is degraded by lysosomal hydrolases and produces small molecules recycled to the cytosol. Created with figdraw.com. PI3P phosphatidylinositol 3-phosphate, PE phosphatidylethanolamine, HOPS homotypic fusion and vacuole protein sorting, RAB targeting GTPase, SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor.
