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
Affiliations
Gaojian Zhang
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Jianxiong Han
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Lili Wang
School of Life Science, Anhui University, Hefei, Anhui 230601, P.R. China
Xuegang Yang
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Zhongkang Yan
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Min Qu
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Huijuan Zhou
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Hazrat Bilal
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Feifei Wang
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China
Honghua Ge
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China; Corresponding author
Xingyuan Yang
Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, P.R. China; Corresponding author
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.
