Mec1-mediated Atg9 phosphorylation regulates the PAS recruitment of Atg9 vesicles upon energy stress.

ABSTRACT: Mec1 plays an essential role in both the DNA damage response and glucose starvation-induced autophagy. We recently reported that Mec1 regulates glucose starvation-induced autophagy through its direct binding to Atg13. However, the role of Mec1's kinase activity in autophagy remains unclear. In this study, we demonstrate that the kinase activity of Mec1 is required for glucose starvation-induced autophagy by regulating the phagophore assembly site (PAS) recruitment of Atg9 vesicles. Mechanistic and functional analyses identified Atg9 as a direct phosphorylation substrate of Mec1, with phosphorylation occurring at the S35, T203, and T243 sites. Mutations at these sites reduce the association of Atg9 with Atg17, Atg23, and Atg27, thereby impairing the PAS recruitment of Atg9 vesicles. Notably

SUBMITTER: Fan S 

PROVIDER: S-EPMC11831128 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature