Figure 2.
Autophagosome formation and lysosomal degradation. Autophagosome formation can be triggered when the mTOR complex is inhibited by various stressors, such as starvation. This induces the assembly of the ULK protein complex composed of ULK1, Atg13 and FIP200 at the isolation membrane, which, in turn, activates the formation of the Beclin-1/PI3KC3 complex composed of Beclin-1, UVRAG, Bif-1, Ambra1, Vps15 and Vps34. During the elongation of the isolation membrane, the Atg5-Atg12-Atg16L1 complex mediates the conjugation of PE to LC3-I, generating LC3-II that relocates from the cytosol to the autophagic membrane and is anchored on its surface. The resulting autophagic membrane structures—autophagosomes—are fused with lysosomes to form autolysosomes, wherein cargoes, including misfolded proteins, are degraded by lysosomal hydrolases.