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

iScience

Xingyuan Yang¹  Gaojian Zhang²  Huijuan Zhou²  Honghua Ge²  Zhongkang Yan²  Feifei Wang²  Jianxiong Han²  Hazrat Bilal²  Xuegang Yang²  Min Qu²  Lili Wang³ 

[1] Corresponding author;Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China;School of Life Science, Anhui University, Hefei, Anhui 230601, P.R. China;

关键词: Biological sciences;    Physiology;    Molecular biology;    Endocrinology;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown