Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis

Biology Direct

Research

Emily Ann Peluso¹  Madelaine C. Brearley-Sholto¹  Thomas Q. de Aguiar Vallim¹  Andrea Raimondi²  Nicolò Ilacqua³  Rana Ghandehari-Alavijeh⁴  Leonardo V. Pellegrini⁴  Danylo Aloshyn⁴  Irene Anastasia⁴  Luca Pellegrini⁵ 

[1] Departments of Medicine/Cardiology and Biological Chemistry, University of California, Los Angeles, CA, USA;Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy;Graduate Program in Neuroscience, Faculty of Medicine, Laval University, Quebec, QC, Canada;Mitochondria Biology Laboratory, Brain Research Center, Laval University, Quebec, QC, Canada;Mitochondria Biology Laboratory, Brain Research Center, Laval University, Quebec, QC, Canada;Mitochondria Biology Laboratory, Brain Research Center, Laval University, Quebec, QC, Canada;Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec, QC, Canada;

关键词: WrappER;    Mitochondria;    Inter-organelle contact;    Synj2bp;    Rrbp1;    ApoE;    MERC;    MAM;    Fatty acid;    VLDL;    Electron microscopy;    NAFLD;    Lipoparticles;   

DOI  :  10.1186/s13062-022-00344-8

 received in 2022-09-09, accepted in 2022-10-26,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundIn mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142–143, 2021; Ilacqua et al. in J Cell Sci 135:1–11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown.MethodsWe evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers.ResultsThe expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration.ConclusionSynj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux.

【 授权许可】

CC BY   
© The Author(s) 2022

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