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Mitochondrial adaptations in skeletal muscle to hindlimb unloading

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Abstract

To gain insight into the regulation of mitochondrial adaptations to hindlimb unloading (HU), the activity of mitochondrial enzymes and the expression of nuclear-encoded genes which control mitochondrial properties in mouse gastrocnemius muscle were investigated. Biochemical and enzyme histochemical analysis showed that subsarcolemmal mitochondria were lost largely than intermyofibrillar mitochondria after HU. Gene expression analysis revealed disturbed or diminished gene expression patterns. The three main results of this analysis are as follows. First, in contrast to peroxisome proliferator-activated receptor γ coactivator 1 β (PGC-1β) and PGC-1-related coactivator, which were down-regulated by HU, PGC-1α was up-regulated concomitant with decreased expression of its DNA binding transcription factors, PPARα, and estrogen-related receptor α (ERRα). Moreover, there was no alteration in expression of nuclear respiratory factor 1, but its downstream target gene, mitochondrial transcription factor A, was down-regulated. Second, both mitofusin 2 and fission 1, which control mitochondrial morphology, were down-regulated. Third, ATP-dependent Lon protease, which participates in mitochondrial-protein degradation, was also down-regulated. These findings suggest that HU may induce uncoordinated expression of PGC-1 family coactivators and DNA binding transcription factors, resulting in reducing ability of mitochondrial biogenesis. Furthermore, down-regulation of mitochondrial morphology-related genes associated with HU may be also involved in alterations in intracellular mitochondrial distribution.

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Acknowledgments

This research was supported by the MEXT (The Ministry of Education, Culture, Sports, Science and Technology) (Grant-in Aid for Scientific Research (C), 22500658), Japan. This research was also partially supported by grants 18A-1 for Nervous and Mental Disorders and H19-kokoro-020 for Research in Brain Science from MHLW (The Ministry of Health, Labour and Welfare), Japan.

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  1. Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, Japan

    Akira Wagatsuma, Takayuki Kawachi, Masataka Shiozuka, Shigeru Yamada & Ryoichi Matsuda

  2. Department of Advanced Interdisciplinary Studies (AIS), Graduate School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan

    Naoki Kotake

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  1. Akira Wagatsuma
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Wagatsuma, A., Kotake, N., Kawachi, T. et al. Mitochondrial adaptations in skeletal muscle to hindlimb unloading. Mol Cell Biochem 350, 1–11 (2011). https://doi.org/10.1007/s11010-010-0677-1

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