Fig. 3.

Autophagosome formation and degradation. a Autophagy involves phagophore-nucleated autophagosome formation, fusion with endolysosomes to form the autolysosome, and subsequent degradation of the autophagosome and its contents by lysosomal hydrolases. Mammalian Atg8 proteins include proteins of the LC3 subfamily, which participate in phagophore elongation, and of the GABARAP subfamily, which coordinate closure of autophagosome. Proper LC3 function is positively and negatively regulated through phosphorylation. Fusion between autophagosome and endolysosomes is coordinated by Pleckhm1, which at the endolysosome binds Rab7 and the HOPS complex, and at the autophagosome binds LC3 and the HOPS complex. The SNARE member Syntaxin17 (STX17) binds autophagosomes through interaction with the endolysosomal SNARE VAMP8, thereby mediating autophagosomal-lysosomal membrane fusion. Autophagosomes and content are then degraded by lysosomal hydrolases. b Cytosolic microtubule-associated protein light chain 3 (LC3)-I is conjugated to phosphatidylethanolamine (PE) to form lipidated LC3-II (LC3-PE), an integral membrane component of the autophagosome and binding partner for autophagy receptors. Two ubiquitin-like conjugation reactions coordinate LC3 lipidation. (1) E1-like and E2-like Atg7 and Atg10 conjugate Atg12 to Atg5, which then complex with Atg16. (2) Pro-LC3 is cleaved at the C-terminus by Atg4, forming LC3-I, which is activated by E1-like Atg7. Through the E2-like Atg3 and E3-like Atg12-Atg5-Atg16 complex, LC3 is lipidated with PE