Figure 1. Molecular components of mammalian autophagic pathways.
Scheme of three different types of autophagy co-existing in mammals. Macroautophagy: A limiting membrane forms de novo engulfing cytosolic components, and seals to form an autophagosome. Degradation occurs when autophagosomes fuse with lysosomes. Initiation of macroautophagy requires assembly and activation of the lipid kinase complex, class III PI3K that serves to recruit components of the two conjugation cascades, the LC3/PE and Atg5/12 cascades to the limiting membrane. Chaperone-mediated autophagy (CMA): When a cytosolic chaperone (hsc70) recognizes a targeting motif (KFERQ) in cytosolic proteins and delivers them to the lysosomal membrane. Upon binding to the lysosome-associated protein type 2A, substrate proteins unfold and cross the lysosomal membrane assisted by a lumenal chaperone. Microautophagy: Invaginations at the lysosomal membrane trap cytosolic cargo that is internalized after the vesicles pinch off into the lysosomal lumen. AA: amino acids; FA: free fatty acids; Atg: autophagy-related protein; PE: phosphatidylethanolamine.