Figure 1.
The autophagic process. Upon deprivation of nutrients or growth factors, activation of AMPK and/or inhibition of mTOR lead to activation of ULK, which phosphorylates Beclin-1, leading to VPS34 activation and phagophore formation. ULK functions in a complex with FIP200 and ATG13, while VPS34 function requires a regulatory subunit, VPS15 (p150), and Beclin-1, which further mediates the association of other regulatory factors such as AMBRA, ATG14, UVRAG and BIF-1. Multiple ATG proteins such as ATG5 and ATG7 constitute two “ubiquitin–like conjugation systems” that catalyze the formation of phosphatidylethanolamine (PE)-conjugated LC3 (LC3-II) and direct its proper incorporation into the phagophore membrane, where it serves as docking site of adaptor proteins (and bound cargos). The closure of an elongated phagophore marks the formation of a mature autophagosome, which eventually fuses with a lysosome, leading to cargo degradation and recycling of nutrients and metabolites. Ub, ubiquitin.
