Fig. 3

Mechanisms of autophagy. The mechanisms of autophagy can be divided into four steps, initiation, nucleation, expansion and closure, and fusion and degradation. In mammals, the assembly of the ULK1/2 complex is necessary for the formation of the phagophore assembly site, whereas the ULK1/2 complex is regulated by mTORC1, which is positively regulated by PI3K/AKT and negatively regulated by AMPK. Growth factors activate the PI3K/Akt pathway through receptor tyrosine kinases (RTKs). The Beclin1 complex, which is usually suppressed by Bcl-2, is activated and drives the isolation membrane to nucleation, and the transmembrane protein Atg9 and vesicle membrane protein VMP1 may be involved in the transport of lipids to the isolation membrane. In addition, two ubiquitin-like protein-conjugated systems (Atg12 and LC3 systems) are needed in this process. Subsequently, the autophagosome and lysosome fusion is mediated by SNARE-like protein, and, finally, various lysosomal enzymes hydrolyze all types of damaged organelles, proteins, lipids, and nucleic acids