Fig. 1

Primary types of autophagy: a schematic overview. Macroautophagy involves the regulation of Unc-51-like kinase 1 (ULK1) complex by both AMPK and mTOR. This complex mediates the initial stage of double-membrane scaffold formation around the autophagy cargo by recruiting the Beclin1-Vps34 complex in the proximity of the phagophore. In the next step of elongation, ATG7-ATG3 and ATG5-ATG12-ATG6L1 complexes mediate the conjugation of lipidated microtubule-associated protein 1A/1B light chain 3 (LC3I) family members with phosphatidylethanolamine (LC3II). Mature autophagosomes fuse with lysosome to form the autophagolysosome, in which autophagic cargo is degraded and recycled. Selective autophagy leads to the degradation of damaged organelles (e.g., pexophagy, ribophagy, lysophagy) or substrates (e.g. aggrephagy, fluidophagy, lipophagy) through the binding of selective receptors with autophagy core proteins (LC3B, GABARAP). Chaperone-mediated autophagy (CMA) is a form of autophagy in which cytoplasmic KFERQ motif proteins are recruited by the Hsc70 chaperone complex. It, then, binds to the lysosome-associated membrane protein type 2 isoform A (LAMP-2A) on the lysosome membrane, which undergoes oligomerization to form a transport channer that mediates the translocation of protein cargo into lysosome for its degradation. Microautophagy, instead, mediates a non-selective up-take of cytoplasmic cargo through invagination (or protrusion) of lysosome membrane. The figure is created with “BioRender.com”