Remodeling of ER‐exit sites initiates a membrane supply pathway for autophagosome biogenesis

摘要

Autophagosomes are double‐membrane vesicles generated during autophagy. Biogenesis of the autophagosome requires membrane acquisition from intracellular compartments, the mechanisms of which are unclear. We previously found that a relocation of COPII machinery to the ER–Golgi intermediate compartment (ERGIC) generates ERGIC‐derived COPII vesicles which serve as a membrane precursor for the lipidation of LC3, a key membrane component of the autophagosome. Here we employed super‐resolution microscopy to show that starvation induces the enlargement of ER‐exit sites (ERES) positive for the COPII activator, SEC12, and the remodeled ERES patches along the ERGIC. A SEC12 binding protein, CTAGE5, is required for the enlargement of ERES, SEC12 relocation to the style="fixed-case">ERGIC, and modulates autophagosome biogenesis. Moreover, style="fixed-case">FIP200, a subunit of the style="fixed-case">ULK protein kinase complex, facilitates the starvation‐induced enlargement of style="fixed-case">ERES independent of the other subunits of this complex and associates via its C‐terminal domain with style="fixed-case">SEC12. Our data indicate a pathway wherein style="fixed-case">FIP200 and style="fixed-case">CTAGE5 facilitate starvation‐induced remodeling of the style="fixed-case">ERES, a prerequisite for the production of style="fixed-case">COPII vesicles budded from the style="fixed-case">ERGIC that contribute to autophagosome formation.