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Hum Mol Genet. 2014 Sep 15;23(18):4770-85. doi: 10.1093/hmg/ddu193. Epub 2014 May 8.

Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis.

Author information

1
Institute of Biochemistry and Molecular Biology.
2
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
3
Department of Life Sciences and Institute of Genome Sciences.
4
Department of Life Sciences and Institute of Genome Sciences Brain Research Center.
5
Center of General Education, Chang Gung University, Taoyuan 333, Taiwan.
6
Department of Life Sciences and Institute of Genome Sciences Brain Research Center Aging and Health Research Center, National Yang-Ming University, Taipei 112, Taiwan Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan joeman@ym.edu.tw joeman@mmc.edu.tw tftsai@ym.edu.tw.
7
Institute of Biochemistry and Molecular Biology Department of Medicine, Mackay Medical College, Sanzhi, New Taipei City 252, Taiwan joeman@ym.edu.tw joeman@mmc.edu.tw tftsai@ym.edu.tw.

Abstract

CISD2 is a causative gene associated with Wolfram syndrome (WFS). However, it remains a mystery as to how the loss of CISD2 causes metabolic defects in patients with WFS. Investigation on the role played by Cisd2 in specific cell types may help us to resolve these underlying mechanisms. White adipose tissue (WAT) is central to the maintenance of energy metabolism and glucose homeostasis in humans. In this study, adipocyte-specific Cisd2 knockout (KO) mice showed impairment in the development of epididymal WAT (eWAT) in the cell autonomous manner. A lack of Cisd2 caused defects in the biogenesis and function of mitochondria during differentiation of adipocytes in vitro. Insulin-stimulated glucose uptake and secretion of adiponectin by the Cisd2 KO adipocytes were decreased. Moreover, Cisd2 deficiency increased the cytosolic level of Ca(2+) and induced Ca(2+)-calcineurin-dependent signaling that inhibited adipogenesis. Importantly, Cisd2 was found to interact with Gimap5 on the mitochondrial and ER membranes and thereby modulate mitochondrial Ca(2+) uptake associated with the maintenance of intracellular Ca(2+) homeostasis in adipocytes. Thus, it would seem that Cisd2 plays an important role in intracellular Ca(2+) homeostasis, which is required for the differentiation and functioning of adipocytes as well as the regulation of glucose homeostasis in mice.

PMID:
24833725
DOI:
10.1093/hmg/ddu193
[Indexed for MEDLINE]

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