Fig. 3

Autophagy-related pathway. Insulin or other growth factors can activate Class I phosphatidylinositol-3 kinase (PI3K)-AKT, thereby activating the mTOR pathway, and AMPK can negatively regulate the mTOR pathway. When activated, AMPK negatively regulates mTOR and activates the UNC-51-like kinase 1 (ULK1) complex, which includes ULK1, autophagy associated protein (ATG) 101, ATG13, and focal adhesion kinase interacting protein of 200 kDa (FIP200). Subsequently, ULK1 phosphorylates ATG14L, promoting the binding of Beclin1 to vacuolar protein sorter 34 (VPS34) to form the Beclin1 complex, which can promote the production of phosphatidylinositol-3-phosphate (PI3P), and thus promote the nucleation of autophagosome membrane. At the same time, the extension of autophagosomes also requires the participation of microtubule-associated protein 1 light chain 3 (LC3). The precursor form of LC3 is cleaved by the protease ATG4B to produce LC3-1. ATG7 and ATG3 are involved in the conversion of LC3-I (free form) to LC3-II (pe conjugated form). After the autophagosome is formed, it fuses with lysosomes to form autophagolysosomes, which eventually participate in autophagy