ATG2A engages Rab1a and ARFGAP1 positive membranes during autophagosome biogenesis.

ABSTRACT: Autophagosomes form from seed membranes that expand through bulk-lipid transport via the bridge-like lipid transporter ATG2. The origins of the seed membranes and their relationship to the lipid transport machinery are poorly understood. Using proximity labeling and a variety of fluorescence microscopy techniques, we show that ATG2A localizes to extra-Golgi ARFGAP1 puncta during autophagosome biogenesis. ARFGAP1 itself is dispensable during macroautophagy, but among other proteins associating to these membranes, we find that Rab1 is essential. ATG2A co-immunoprecipitates strongly with Rab1a, and siRNA-mediated depletion of Rab1 blocks autophagy downstream of LC3B lipidation, similar to ATG2A depletion. Further, when either autophagosome formation or the early secretory pathway is perturbed

SUBMITTER: Fuller DM 

PROVIDER: S-EPMC11974814 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature