Fig. 1

Mechanisms of macroautophagy. Stress signals activate AMPK and inhibits mTORC1. mTORC1 is inhibited by AMPK and activated by growth factor induced PI3K-Akt pathway that initiates autophagy. 1. Initiation: Activated AMPK and inhibited mTORC1 initiates ULK complex. 2. Nucleation: ULK complex recruits kinase complex to the PAS that results in the production of PI3P at the isolation membrane. 3. Elongation: PI3P recruits downstream Atg proteins for elongation of the membrane. Atg12–5 forms a complex with Atg16L1 that associates with isolation membrane. The Atg12–5-16 L1 complex along with Atg7 and Atg3 are required for the formation of LC3-II from LC3-I. The LC3-II mediates the elongation and completion of the autophagosome. 4. Fusion: Autophagosome fuses with the lysosome to form the autolysosome. Lysosomal enzymes degrade the contents of the autolysosome. In selective autophagy, adaptor proteins like p62 binds to ubiquitinated proteins and organelles, attaches them with LC3-II and brings them in the autophagosome for degradation