Fig. 1

Overview of the autophagy process and regulatory mechanism. Autophagy consists of five main steps: initiation, phagophore nucleation, vesicle elongation, docking, and fusion and degradation. Autophagy is triggered by various stresses, such as hypoxia, oxidative stress, or energy nutrient deprivation. Under these conditions, the AMPK signaling is activated, which results in the dissociation of the ULK1/2 complex (comprising ULK1/2, ATG101, FIP200 and ATG13) from the mTORC1 complex (including GβL, mTOR, and Raptor), thereby promoting phagophore nucleation by the phosphorylating PI3KC3 complex (comprising Beclin1, AMBRA1, VPS15, VPS34, and ATG14L), and the production of local PtdIns3P in the omegasome. PtdIns3P then recruits PtdIns3P-binding proteins, such as WIPIs, DFCP1 and ATG9 vesicles, for phagophore expansion. Two ubiquitin-like conjugation systems are involved in vesicle elongation and autophagasome formation. In one system, the ATG12-ATG5-ATG16L complex (E3) is formed under the catalysis of ATG7 (E1-like enzyme) and ATG10 (E2-like enzyme). In the other system, cytosolic LC3-I is conjugated to phosphatidylethanolamine (PE) under the catalysis of protease ATG4, ATG3 and ATG7 to form membrane-bound LC3-PE complex (LC-II). Finally, a large group of molecules, including SNARE complex, HOPS complex, RAB GTPases and adaptors, cytoskeleton components, and related motor proteins, promote the fusion of the autophagosome and lysosome to form autolysosome, where the inner autophagosomal membrane and sequestered contents are degraded by lysosomal hydrolases and released for reutilization