Figure 3.

Autophagy. In response to nutrient deprivation, inhibition of ULK1-FIP200-ATG13 complex by mTORC1 is removed. ULK1 autophosphorylates and activates ATG13 and FIP200. AMPK, activated in response to starvation, contributes by phosphorylating and inhibiting components of the mTORC1 complex and phosphorylating and further activating ULK1. ULK1 subsequently phosphorylates Beclin-1 and Vps34 resulting in nucleation of the isolation membrane. Inhibitory phosphorylation of Vsp34 by AMPK is prevented by recruiting ATG14L to the complex and AMPK then phosphorylates and further activates Beclin-1. Lipids are recruited to the growing phagophore and two ubiquitin-like conjugation pathways are triggered resulting in an ATG12-ATG5-ATG16 complex at the autophagosome and LC3-II insertion into the membrane, where it recruits cargo. Lysosomes dock to the outer membrane of the autophagosome forming an autolysosome, and allowing hydrolases to degrade its contents.