Fig. 2

The types and processes of autophagy

Autophagy is mainly divided into three classical types, namely macroautophagy, microautophagy, and CMA. ①Macroautophagy: The procedures of macroautophagy can be characterized by initiation, elongation/closure, and maturation according to the obvious morphological changes in vesicular compartments. PGs are formed from intracellular membranes regulated by ULK1 complex and class III PI3K complex, and subsequently, they are transformed into AVs enriching the LC3-II regulated by the conserved autophagy genes. Macroautophagy was considered to be a process that disposes cytoplasmic components into AVs randomly and nonselectively, whereas the selective function of AVs has been garnering increasing attention recently. In selective autophagy, cargo is linked to AVs by a physical combination of SARs and LC3-II through the LIR motif and recognized in an Ub-dependent or Ub-independent manner. Finally, the autophagosomes fuse with the lysosomes to form the autolysosomes where the cargoes are degraded and the degradative products released back into the cytosol are reused. ②Microautophagy: Cargoes, including proteins and organelles, are sequestered and degraded in bulk through direct invagination into the lysosome. ③CMA: The cytosolic substrates containing the pentapeptide KFERQ motif are transferred to the lysosome for internalization and degradation when they are recognized in an HSPA8/HSC70 chaperone-dependent manner and thus bind with the LAMP-2 A multimeric complex on the lysosomal membrane

Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; ATG: autophagy-related; AVs: autophagic vesicles; CMA: chaperone-mediated autophagy; FIP2000: focal adhesion kinase family interacting protein of 200kDa; LAMP-2A: lysosomal-associated membrane protein 2A; LC3-II: LC3 lipid; LIR: LC3/GABARAP-interacting region; mTOR, mechanistic target of rapamycin; NSP, nonstructural protein; PE: phosphatidylethanolamine; PGs: phagephore; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PI3K: phosphoinositide 3-kinase; SARs: selective autophagy receptors; Ub: ubiquitin; UBD: ubiquitin binding domain; ULK, unc-51 like autophagy activating kinase