フジタ　トシハル   Toshiharu Fujita   藤田　敏治    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy.
掲載誌名	正式名：Nature communications 略　 称：Nat Commun ISSNコード：20411723/20411723
掲載区分	国外
巻・号・頁	15(1),pp.7194
著者・共著者	Keisuke Tabata, Kenta Imai, Koki Fukuda, Kentaro Yamamoto, Hayato Kunugi, Toshiharu Fujita, Tatsuya Kaminishi, Christian Tischer, Beate Neumann, Sabine Reither, Fatima Verissimo, Rainer Pepperkok, Tamotsu Yoshimori, Maho Hamasaki
発行年月	2024/08
概要	Autophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by a double-membrane organelle called autophagosome and degrading materials by fusing with the lysosome. The process of autophagy is regulated by sequential recruitment and function of autophagy-related (Atg) proteins. Genetic hierarchical analyses show that the ULK1 complex comprised of ULK1-FIP200-ATG13-ATG101 translocating from the cytosol to autophagosome formation sites as a most upstream ATG factor; this translocation is critical in autophagy initiation. However, how this translocation occurs remains unclear. Here, we show that ULK1 is palmitoylated by palmitoyltransferase ZDHHC13 and translocated to the autophagosome formation site upon autophagy induction. We find that the ULK1 palmitoylation is required for autophagy initiation. Moreover, the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate, one of the autophagosome membrane's lipids. Our results reveal how the most upstream ULK1 complex translocates to the autophagosome formation sites during autophagy.
DOI	10.1038/s41467-024-51402-w
PMID	39169022