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

Chih Hao Wang, Yi Fan Chen, Chia Yu Wu, Pei Chun Wu, Yi Long Huang, Cheng Heng Kao, Chao Hsiung Lin, Lung Sen Kao, Ting Fen Tsai, Yau Huei Wei

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44 Citations (Scopus)

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 Ca2+ and induced Ca2+-calcineurin-dependent signaling that inhibited adipogenesis. Importantly, Cisd2 was found to interact with Gimap5 on the mitochondrial and ER membranes and thereby modulate mitochondrial Ca2+ uptake associated with the maintenance of intracellular Ca2+ homeostasis in adipocytes. Thus, it would seem that Cisd2 plays an important role in intracellular Ca2+ homeostasis, which is required for the differentiation and functioning of adipocytes as well as the regulation of glucose homeostasis in mice.

Original languageEnglish
Article numberddu193
Pages (from-to)4770-4785
Number of pages16
JournalHuman Molecular Genetics
Volume23
Issue number18
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

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    Wang, C. H., Chen, Y. F., Wu, C. Y., Wu, P. C., Huang, Y. L., Kao, C. H., Lin, C. H., Kao, L. S., Tsai, T. F., & Wei, Y. H. (2014). Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. Human Molecular Genetics, 23(18), 4770-4785. [ddu193]. https://doi.org/10.1093/hmg/ddu193