The vesicular transporter STX11 governs ATGL-mediated hepatic lipolysis and lipophagy

Autor: Gaojian Zhang, Jianxiong Han, Lili Wang, Xuegang Yang, Zhongkang Yan, Min Qu, Huijuan Zhou, Hazrat Bilal, Feifei Wang, Honghua Ge, Xingyuan Yang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 4, Pp 104085- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.104085
Popis: Summary: Hepatic lipid accumulation is closely associated with nonalcoholic fatty liver disease (NAFLD). Adipose-triglyceride-lipase (ATGL) regulates triglyceride hydrolysis and maintains energy homeostasis in hepatocytes. Identifying key factors in the regulation of ATGL will help tackle hepatic lipid accumulation and related metabolic diseases. Herein, we demonstrate that syntaxin11 (STX11), a member of the SNARE family, generally expressed in immune cells, mediates lipid metabolism by binding to ATGL and inhibiting lipid droplet degradation and lipid autophagy in hepatocytes. Our data show that the C-terminal of STX11 and the patatin domain-containing segment of ATGL have direct physical interactions. Thus, STX11 overexpression prevents spatial translocation of ATGL onto LDs by recruitment of ATGL to the ER. Conversely, STX11 deficiency in hepatocytes promotes lipid hydrolysis, and the ATGL-SIRT1 signaling pathway enhances lipophagy. Overall, this study uncovered that the regulation of lipolysis and lipophagy is achieved by STX11 through the attenuation of ATGL action in hepatocytes.
Databáze: Directory of Open Access Journals