OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis
Tianming Wang,
Qinjun Wei,
Lihong Liang,
Xujun Tang,
Jun Yao,
Yajie Lu,
Yuan Qu,
Zhibin Chen,
Guangqian Xing,
Xin Cao
Affiliations
Tianming Wang
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China
Qinjun Wei
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China; The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
Lihong Liang
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China
Xujun Tang
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China
Jun Yao
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China
Yajie Lu
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China
Yuan Qu
Jiangsu Cancer Hospital, Nanjing 210009, China
Zhibin Chen
Department of Otolaryngology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Guangqian Xing
Department of Otolaryngology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Xin Cao
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China; The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China; Corresponding author
Summary: The accumulation of giant lipid droplets (LDs) increases the risk of metabolic disorders including obesity and insulin resistance. The lipolysis process involves the activation and transfer of lipase, but the molecular mechanism is not completely understood. The translocation of ATGL, a critical lipolysis lipase, from the ER to the LD surface is mediated by an energy catabolism complex. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is one of the lipid transfer proteins that regulates intracellular cholesterol homeostasis. A recent study has proven that Osbpl2−/− pigs exhibit hypercholesterolemia and obesity phenotypes with an increase in adipocytes. In this study, we identified that OSBPL2 links the endoplasmic reticulum (ER) with LDs, binds to COPB1, and mediates ATGL transport. We provide important insights into the function of OSBPL2, indicating that it is required for the regulation of lipid droplet lipolysis.
