Figure 2.

Autophagy process and molecular actors. Several external stimuli activate the ULK1/2 complex, which initiates isolation membrane near material to be removed. After this initiation step, the nucleation relies on the association of Beclin1 with class III phosphatidyl-inositol 3 kinase (PI3K III) to initiate phagophore formation. Other proteins like UVRAG, Bif-1 and AMBRA1 can also join this complex. The Atg5-Atg12-Atg16L complex and LC3 are two conjugation systems promoting the elongation of the phagophore to form the autophagosome, a vesicle containing the autophagic cargos. Cytosolic-free LC3, named LC3I, is transformed into LC3II, which consists of LC3 covalently bound to a phosphatidyl-ethanolamine molecule. LC3II is then anchored to the pre-autophagosomal membrane. After the binding of certain cytosolic cargos, the p62 protein leads them to the autophagosome, facilitating their degradation by autophagy. Thereafter, the autophagosome fuses with a lysosome to form the autophagolysosome, then the autophagic cargos are degraded by the lysosomal enzymes. Until its degradation, the p62 protein remains associated with the autophagosome