The COPII coat protein SEC24D is required for autophagosome closure in mammals.

Macroautophagy involves the encapsulation of cellular components within double-membrane autophagosomes for subsequent degradation in vacuoles or lysosomes. Coat protein complex II (COPII) vesicles serve as a membrane source for autophagosome formation. However, the specific role of SEC24D, an isoform of the COPII coat protein SEC24, in the macroautophagy pathway remains unclear. In this study, we demonstrate that SEC24D is indispensable for macroautophagy and important for autophagosome closure. Depletion of SEC24D leads to the accumulation of unsealed isolation membranes. Furthermore, under conditions of starvation, SEC24D interacts with casein kinase1 delta (CK1δ), a member of the casein kinase 1 family, and autophagy-related 9A (ATG9A). Collectively, our findings unveil the indispensable role of SEC24D in starvation-induced autophagy in mammalian cells.