Chchd10 is dispensable for myogenesis but critical for adipose browning

Cell Regeneration
Wei Xia1, Jiamin Qiu2, Ying Peng2, Madigan M. Snyder3, Li Gu2, Kuilong Huang2, Nanjian Luo2, Yue Feng2, Shihuan Kuang4
1College of Animal Science and Technology,Hebei Agricultural University, Baoding 071000, China
2Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA
3Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA
4Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 USA

Tóm tắt

AbstractThe Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus. Mutations of Chchd10 are associated with ALS, dementia and myopathy in humans and animal models, but how knockout of Chchd10 (Chchd10KO) affects various tissues especially skeletal muscle and adipose tissues remains unclear. Here we show that Chchd10 expression increases as myoblasts and preadipocytes differentiate. During myogenesis, CHCHD10 interacts with TAR DNA binding protein 43 (TDP-43) in regenerating myofibers in vivo and in newly differentiated myotubes ex vivo. Surprisingly, Chchd10KO mice had normal skeletal muscle development, growth and regeneration, with moderate defects in grip strength and motor performance. Chchd10KO similarly had no effects on development of brown and white adipose tissues (WAT). However, Chchd10KO mice had blunted response to acute cold and attenuated cold-induced browning of WAT, with markedly reduced UCP1 levels. Together, these results demonstrate that Chchd10 is dispensable for normal myogenesis and adipogenesis but is required for normal motility and cold-induced, mitochondrion-dependent browning of adipocytes. The data also suggest that human CHCHD10 mutations cause myopathy through a gain-of-function mechanism.

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Cell Regeneration

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