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

Gaojian Zhang; Jianxiong Han; Lili Wang; Xuegang Yang; Zhongkang Yan; Min Qu; Huijuan Zhou; Hazrat Bilal; Feifei Wang; Honghua Ge; Xingyuan Yang

doi:10.1016/j.isci.2022.104085

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

iScience. 2022 Mar 16;25(4):104085. doi: 10.1016/j.isci.2022.104085. eCollection 2022 Apr 15.

Authors

Affiliations

¹ Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China.
² School of Life Science, Anhui University, Hefei, Anhui 230601, P.R. China.

Abstract

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.

Keywords: Biological sciences; Cell biology; Endocrinology; Molecular biology; Physiology.