FIGURE 1.

Role and regulation of the overall autophagy process. The initiation of autophagy is dependent on nutrient deprivation or growth factors that activate AMPK or inhibit mTORC1, thus stimulating the ULK1 complex (ATG13 and FIP200). The phosphorylation of Beclin-1 leads to the activation of VPS34, which stimulates phagophore initiation and formation. Atg5–Atg12 conjugation stimulates Atg7 and Atg10 to form the Atg12–Atg5–Atg16 complex, which ultimately influences phagophore formation. The Atg7, Atg3, and Atg16 complex has a function similar to that of E3 in the direction of the LC3-PE association (LC3-II) for formation of the autophagosome. The maturation of the autophagosome involves fusion to lysosomes via ESCRT, SNARE, and Rab7. Lysosome binds to autophagosome by several lysosomal proteins leading to cargo degradation as well as metabolite production and recycling of nutrient products (Rahman and Rhim, 2017).