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Effect of Alisporivir on Calcium Ion Transport and Mitophagy in Skeletal Muscle and Heart Mitochondria in Dystrophin-Deficient Mice

  • BIOPHYSICS AND BIOCHEMISTRY
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Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of the mitochondrial calcium-dependent pore (MPT pore) inhibitor alisporivir (5 mg/kg per day for 4 weeks) on the parameters of calcium ion transport and the intensity of mitophagy in mitochondria of the heart and skeletal muscles of dystrophin-deficient C57BL/10ScSn-mdx mice. Alisporivir increased the rate of calcium uptake by skeletal muscle mitochondria of mdx mice, which was accompanied by changes in the level of the MCU and MCUb subunits of the calcium uniporter. At the same time, the intensity of calcium uniport in the heart mitochondria did not change. Alisporivir was found to reduce the expression of Pink1 and Parkin genes regulating the intensity of mitophagy in skeletal muscles of mdx mice, but did not affect the expression of these genes in the heart. This effect of alisporivir was accompanied by fragmentation and a decrease in the mean size of organelles. Possible mitochondrion-related mechanisms of the protective effect of alisporivir on the skeletal muscle and heart cells are discussed.

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Authors and Affiliations

  1. Mari State University, Yoshkar-Ola, the Mari El Republic, Russia

    M. V. Dubinin, V. S. Starinets & K. N. Belosludtsev

  2. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region, Russia

    V. S. Starinets, I. B. Mikheeva & K. N. Belosludtsev

Authors
  1. M. V. Dubinin
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  2. V. S. Starinets
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  3. I. B. Mikheeva
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  4. K. N. Belosludtsev
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Correspondence to M. V. Dubinin.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 172, No. 12, pp. 691-697, December, 2021

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Dubinin, M.V., Starinets, V.S., Mikheeva, I.B. et al. Effect of Alisporivir on Calcium Ion Transport and Mitophagy in Skeletal Muscle and Heart Mitochondria in Dystrophin-Deficient Mice. Bull Exp Biol Med 172, 695–700 (2022). https://doi.org/10.1007/s10517-022-05459-6

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  • DOI: https://doi.org/10.1007/s10517-022-05459-6

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