Macroautophagy. (a) Macroautophagy involves the formation of a double-membrane vesicle called the autophagosome. This structure sequesters damaged organelles and misfolded proteins that are degraded by lysosomal enzymes. (b) The Initiation step is controlled by the ULK1-Atg13-FIP200 complex, which also contains Atg101. mTOR interacts with and inactivates ULK1 by phosphorylation. Under starvation conditions, mTOR is inactivated leading to ULK1 activation, phosphorylation of Atg13 and FIP200, and consequently the induction of autophagy. The Nucleation step requires the Beclin-1-class III PI3K complex including Beclin-1, class III PI3K, Vps15, Atg14L, and Ambra1. The ULK1-Atg13-FIP200 and Beclin-1-class III PI3K complexes recruit two conjugation systems essential for the elongation and enclosure step: the Atg12-Atg5 and the Atg8-PE conjugation systems. PE: phosphatidylethanolamine.
