Acetylation of STX17 promotes its autophagosomal translocation.

Autophagy is a fundamental process for maintaining cell homeostasis, and STX17-mediated autophagosome-lysosome fusion is essential for cargo degradation and recycling. The translocation of STX17 to the autophagosome membrane is necessary for the fusion, yet the mechanism governing this process remains to be fully elucidated. Here, we show that following starvation, STX17 is acetylated at lysine 254 (K254), and this promotes the autophagosomal translocation of STX17 and subsequent autophagosome-lysosome fusion. Acetyltransferase GCN5 mediates STX17 K254 acetylation, which is counteracted by the deacetylase SIRT1. Moreover, autophagosomal translocation of K254-acetylated STX17 is mediated by myosin Ⅵ. Therefore, our research highlights the importance of acetylation and F-actin-based motor proteins in autophagosomal translocation of STX17 and autophagosome-lysosome fusion.