Fig. 4.

The core molecular mechanisms of autophagy. Autophagy can be divided into three stages: the induction stage, the formation stage of autophagosomes, and the formation of autophagic lysosomes and the degradation of their contents. 1. Autophagy induction stage: The ULK1-Atg13-Atg101-FIP200 complex transmits autophagy signals to the nucleus, and the Class III PI3K-Beclin-1 complex induces the formation of a double-layer membrane, leading to the accumulation of phagocytic vesicles. 2. Formation of the autophagosome: On the one hand, Atg7 and Atg10 activate and transport Atg12, which in turn binds to Atg5 and Atg16 to form the Atg5-Atg12-Atg16 complex. On the other hand, LC3 is decomposed by Atg4 to form LC3-I, which is activated by Atg7 and Atg3 and accumulates on the autophagosome membrane under the induction of the Atg5-Atg12-Atg16 complex to form LC3-II. The membrane extends and surrounds the intracellular degradation substrate to form an autophagosome. 3. Formation of autophagosomes and degradation of their contents: Through the interaction of LAMP-1, LAMP-2, GTPase-RAB-7, and other proteins, autophagosomes fuse with lysosomes to form autophagosomes, which release hydrolytic enzymes to fully degrade substrates. Abbreviations: Atg, Autophagy-related gene; LC3, microtubule-associated protein light-chain 3; PI3K, phosphoinositide 3-kinase; LAMP, lysosome-associated membrane protein; GTPase, GTP hydrolase; RAB-7, ras-related protein Rab-7