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Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle

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Abstract

The abundance, morphology, and functional properties of mitochondria become altered in response to denervation. To gain insight into the regulation of this process, mitochondrial enzyme activities and gene expression involved in mitochondrial biogenesis and dynamics in mouse gastrocnemius muscle was investigated. Sciatic nerve transactions were performed on mice, and then gastrocnemius muscles were isolated at days 5 and 30 after surgery. Muscle weight was decreased significantly by 15% and 62% at days 5 and 30 after surgery, respectively. The activity of citrate synthase, a marker of oxidative enzyme, was reduced significantly by 31% and 53% at days 5 and 30, respectively. Enzyme histochemical analysis revealed that subsarcolemmal mitochondria were largely lost than intermyofibrillar mitochondria at day 5, and this trend was further progressed at day 30 after surgery. Expression levels of peroxisome proliferator-activated receptor, γ coactivator 1 (PGC-1)α, estrogen-related receptor α (ERRα), and mitofusin 2 were down-regulated throughout the experimental period, whereas those of PGC-1β, PRC, nuclear respiratory factor (NRF)-1, NRF-2, TFAM, and Lon protease were down-regulated at day 30 after surgery. These results suggest that PGC-1α, ERRα, and mitofusin 2 may be important factors in the process of denervation-induced mitochondrial adaptation. In addition, other PGC-1 family of transcriptional coactivators and DNA binding transcription factors may also contribute to mitochondrial adaptation after early response to denervation.

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Acknowledgement

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.

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Authors and Affiliations

  1. Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan

    Akira Wagatsuma & Shigeru Yamada

  2. Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan

    Akira Wagatsuma & Kunihiko Mabuchi

  3. Department of Advanced Interdisciplinary Studies (AIS), Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

    Naoki Kotake

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  1. Akira Wagatsuma
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Correspondence to Akira Wagatsuma.

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Wagatsuma, A., Kotake, N., Mabuchi, K. et al. Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle. J Physiol Biochem 67, 359–370 (2011). https://doi.org/10.1007/s13105-011-0083-5

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