Figure 2.

Schematic representation of the autophagy process. The autophagy mechanism consists of five phases. In the initiation phase, mTORC1 is inactivated due to autophagy-stimulating signals, liberating the repression of the ULK1 complex. During the nucleation phase, the ULK1 complex phosphorylates the PI3KC3 complex, which induces phagophore formation in the omegasome, through the production of PI3P and association with WIPI protein family members, commonly WIPI2. In the elongation phase, two ubiquitin-like protein systems, ATG12-ATG5-ATG16L1 and ATG4B-ATG7-ATG3, mediate the activation of LC3 into LC3I, lipidation with PE to form LC3II, and subsequent anchoring to the phagophore. GABARAP also conjugates with PE and attaches to the membrane. LC3 and GABARAP mediate the sequestration of autophagic substrates marked with SARs, such as p62/SQSTM1, before phagophore closure and total autophagosome development. During the fusion phase, STX17 and VAMP8, present in the autophagosome and lysosome, respectively, interact and stimulate autolysosome formation. Finally, in the degradation phase, acidic lysosomal hydrolases degrade autophagic cargo, generating nutrients that are released to the cytoplasm and reused by the cell. ER, endoplasmic reticulum.