• Meilian Liu, Hongzhi Chen, Li Wei, Derong Hu, Kun Dong, Weiping Jia, Lily Q Dong, and Feng Liu.
• From the Metabolic Syndrome Research Center, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China, the Departments of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131.
• J. Biol. Chem. 2015 Apr 17; 290 (16): 10143-8.

AbstractAdiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions. We previously reported that adiponectin multimerization and stability are promoted by the disulfide bond A oxidoreductase-like protein (DsbA-L) in cells and in vivo. However, the precise mechanism by which DsbA-L regulates adiponectin biosynthesis remains elusive. Here we show that DsbA-L is co-localized with the endoplasmic reticulum (ER) marker protein disulfide isomerase and the mitochondrial marker MitoTracker. In addition, DsbA-L interacts with the ER chaperone protein Ero1-Lα in 3T3-L1 adipocytes. In silico analysis and truncation mapping studies revealed that DsbA-L contains an ER targeting signal at its N terminus. Deletion of the first 6 residues at the N terminus greatly impaired DsbA-L localization in the ER. Overexpression of the wild type but not the ER localization-defective mutant of DsbA-L protects against thapsigargin-induced ER stress and adiponectin down-regulation in 3T3-L1 adipocytes. In addition, overexpression of the wild type but not the ER localization-defective mutant of DsbA-L promotes adiponectin multimerization. Together, our results reveal that DsbA-L is localized in both the mitochondria and the ER in adipocytes and that its ER localization plays a critical role in suppressing ER stress and promoting adiponectin biosynthesis and secretion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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