Fig. 2.

Fasting mediates autophagy. Autophagy receives fasting signals through two metabolic sensors such as mTOR and AMPK. Under the condition of nutrient depletion, mTOR detaches from the ULK1 complex leading to the activation of autophagy. Whereas, AMPK negatively regulates mTOR, and also directly activates ULK1 complex, thereby acting as a positive regulator of autophagy in response to nutrient depletion. Beclin1 complex is another autophagy activator that is negatively regulated by mTOR. Once autophagy is initiated, cytoplasmic elements (cargo) to be recycled are engulfed into double-membrane vesicles, termed as autophagosomes, which fuse with lysosomes forming autolysosomes, where cargos are degraded. Autophagy is a multistep process that includes (1) initiation, (2) membrane nucleation and phagophore formation, (3) phagophore elongation, (4) docking and fusion with the lysosome, and (5) degradation, which are regulated by autophagy-related proteins (ATGs). mTOR, mechanistic target of rapamycin; AMPK, AMP-activated protein kinase.