期刊
AUTOPHAGY
卷 17, 期 7, 页码 1684-1699出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2020.1781393
关键词
ATG13; autophagosome; autophagy; linear ubiquitination; LUBAC; OTULIN; RNF31
类别
资金
- National Natural Science Foundation of China [31570781, 31770831]
- ShanghaiTech University [2015F0202-000-31]
The study reveals that LUBAC and OTULIN cooperatively regulate autophagy initiation and autophagosome maturation by mediating the linear ubiquitination and stabilization of ATG13.
Macroautophagy/autophagy is a membrane-mediated intracellular degradation pathway, through which bulky cytoplasmic content is digested in lysosomes. How the autophagy initiation and maturation steps are regulated is not clear. In this study, we found an E3 ubiquitin ligase complex, linear ubiquitin chain assembly complex (LUBAC) and a deubiquitinating enzyme (DUB) OTULIN localize to the phagophore area to control autophagy initiation and maturation. LUBAC key component RNF31/HOIP translocates to the LC3 puncta area when autophagy is induced.RNF31knockdown inhibits autophagy initiation, and cells are more sensitive to bacterial infection.OTULINknockdown, however, promotes autophagy initiation but blocks autophagy maturation. InOTULINknockdown cells, excessive ubiquitinated ATG13 protein was recruited to the phagophore for prolonged expansion, and therefore inhibits autophagosome maturation. Together, our study provides evidence that LUBAC and OTULIN cooperatively regulate autophagy initiation and autophagosome maturation by mediating the linear ubiquitination and the stabilization of ATG13.
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