Fig. 1.

Steps of autophagy induction and autophagosome formation. Mammalian target of rapamycin complex 1 (mTORC1) inhibition by nutrient deprivation or rapamycin treatment induces the dephosphorylation of UNC51-like kinase 1 (ULK1), which phosphorylates autophagy-related gene 13 (Atg13) and FIP200. When autophagy is activated, Beclin 1 is liberated from Bcl-2 and induces autophagosome formation with Vps34, Vps15, and Atg14L or autophagosome maturation with Vps34, Vps15, and ultraviolet radiation resistance-associated gene (UVRAG). Phosphatidylinositol-3-phosphate (PI3P) produced by Vps34 is important in the recruitment of Atg proteins to initiate autophagosome formation. The Atg system is similar to the ubiquitination system. Atg12 and light chain 3 (LC3) are ubiquitin-like proteins. Atg7 is similar to E1. Atg10 and Atg 3 are E2-like enzymes. The Atg12-Atg5-Atg16L1 complex behaves like E3 ligase. LC3-II, formed by LC3 conjugation to its lipid target (phosphatidylethanolamine, PE), is a receptor for p62 which binds to ubiquitinated proteins for proteolytic degradation.