Figure 1.

Schematic representation of regulatory pathways involved in the autophagic event and point of inhibition/activation. Under a deprivation of nutrients or growth factors, ULK activation occurs via the activation of activating AMP kinase (AMPK) and/or the inhibition of mTOR. ULK functions in a complex with FIP200 and Atg13, which phosphorylates Beclin-1, leading to VPS34 activation and phagophore formation. Association between Beclin-1 and Bcl-2 inhibits autophagy. Two ubiquitin-like conjugation systems are engaged, one involving Atg12, Atg5, and Atg16L proteins, and the other converting LC3 protein from its LC3I form to LC3II. This event leads to closure of an elongated phagophore with the formation of a mature autophagosome, which is followed by transport of the autophagic cargo to lysosomes, degradation of this cargo by lysosomal hydrolases, and recycling of the products for use in metabolism.