上海科技大学知识管理系统

The selective removal of damaged or unnecessary proteins and organelles via autophagy is an essential for maintaining cellular homeostasis during starvation. COPI vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi apparatus to the endoplasmic reticulum, with COPI-associated SCYL1 facilitates this trafficking. While COPI vesicles are implicated in autophagosome formation, the mechanisms underlying this contribution remain poorly understood. In this study, we used APEX2-based proximity labeling to identify proteins associated with membrane-conjugated LC3 in selective autophagy, revealing several candidates, including SCYL1. SCYL1 functions as a Golgiphagy receptor, mediating the autophagic degradation of Golgi components during starvation in a COPI-dependent manner. SCYL1 interacts with LC3 through an LIR motif to mediate COPI cargos for autophagic degradation, and defects in this motif leads to impaired Golgiphagy. Furthermore, SCYL1 enhances the recruitment of early autophagy-related proteins to COPI vesicles, promoting autophagosome formation. Notably, this process is inhibited by the phosphorylation of SCYL1 by the mTORC1 kinase. Under starvation conditions, mTORC1 inhibition reduces phosphorylation of SCYL1, which in turn enhances its interaction with LC3 and potentiates its role as a Golgiphagy receptor. Transcriptomic analyses and SCYL1 interactome profiling reveal significant alterations in multiple genes associated with membrane trafficking following SCYL1 knockdown. Taken together, our findings establish SCYL1 as a novel Golgiphagy receptor that facilitates COPI vesicle in mediating autophagosome formation under stress.