FIG 7.

Model of ULK1- and AMPK-mediated regulation of Atg9A via phosphorylation at S761. Under nutrient-replete conditions, a low level of phosphorylation is dependent on ULK1 and AMPK, suggesting a relationship between these kinases under basal conditions (42). We favor the hypothesis that AMPK is directly responsible for Atg9A phosphorylation, with ULK1 playing an ancillary role (see Discussion). We posit that this low level of phosphorylation maintains a basal level of autophagy. Under nutrient deprivation, an increased AMP-to-ADP ratio results in the full activation of AMPK and increased phosphorylation at S761 independent of ULK1, leading to increased autophagy, localization of Atg9A to autophagosomes, and autophagosome biogenesis.