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Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differenti...

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Autores principales: Oikawa, Yoshitsugu, Izumi, Rumiko, Koide, Masashi, Hagiwara, Yoshihiro, Kanzaki, Makoto, Suzuki, Naoki, Kikuchi, Koichi, Matsuhashi, Tetsuro, Akiyama, Yukako, Ichijo, Mariko, Watanabe, Shun, Toyohara, Takafumi, Suzuki, Takehiro, Mishima, Eikan, Akiyama, Yasutoshi, Ogata, Yoshiaki, Suzuki, Chitose, Hayashi, Hironori, Kodama, Eiichi N., Hayashi, Ken-ichiro, Itoi, Eiji, Aoki, Masashi, Kure, Shigeo, Abe, Takaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710105/
https://www.ncbi.nlm.nih.gov/pubmed/33264289
http://dx.doi.org/10.1371/journal.pone.0231064
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author Oikawa, Yoshitsugu
Izumi, Rumiko
Koide, Masashi
Hagiwara, Yoshihiro
Kanzaki, Makoto
Suzuki, Naoki
Kikuchi, Koichi
Matsuhashi, Tetsuro
Akiyama, Yukako
Ichijo, Mariko
Watanabe, Shun
Toyohara, Takafumi
Suzuki, Takehiro
Mishima, Eikan
Akiyama, Yasutoshi
Ogata, Yoshiaki
Suzuki, Chitose
Hayashi, Hironori
Kodama, Eiichi N.
Hayashi, Ken-ichiro
Itoi, Eiji
Aoki, Masashi
Kure, Shigeo
Abe, Takaaki
author_facet Oikawa, Yoshitsugu
Izumi, Rumiko
Koide, Masashi
Hagiwara, Yoshihiro
Kanzaki, Makoto
Suzuki, Naoki
Kikuchi, Koichi
Matsuhashi, Tetsuro
Akiyama, Yukako
Ichijo, Mariko
Watanabe, Shun
Toyohara, Takafumi
Suzuki, Takehiro
Mishima, Eikan
Akiyama, Yasutoshi
Ogata, Yoshiaki
Suzuki, Chitose
Hayashi, Hironori
Kodama, Eiichi N.
Hayashi, Ken-ichiro
Itoi, Eiji
Aoki, Masashi
Kure, Shigeo
Abe, Takaaki
author_sort Oikawa, Yoshitsugu
collection PubMed
description Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.
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spelling pubmed-77101052020-12-03 Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5 Oikawa, Yoshitsugu Izumi, Rumiko Koide, Masashi Hagiwara, Yoshihiro Kanzaki, Makoto Suzuki, Naoki Kikuchi, Koichi Matsuhashi, Tetsuro Akiyama, Yukako Ichijo, Mariko Watanabe, Shun Toyohara, Takafumi Suzuki, Takehiro Mishima, Eikan Akiyama, Yasutoshi Ogata, Yoshiaki Suzuki, Chitose Hayashi, Hironori Kodama, Eiichi N. Hayashi, Ken-ichiro Itoi, Eiji Aoki, Masashi Kure, Shigeo Abe, Takaaki PLoS One Research Article Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM. Public Library of Science 2020-12-02 /pmc/articles/PMC7710105/ /pubmed/33264289 http://dx.doi.org/10.1371/journal.pone.0231064 Text en © 2020 Oikawa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Oikawa, Yoshitsugu
Izumi, Rumiko
Koide, Masashi
Hagiwara, Yoshihiro
Kanzaki, Makoto
Suzuki, Naoki
Kikuchi, Koichi
Matsuhashi, Tetsuro
Akiyama, Yukako
Ichijo, Mariko
Watanabe, Shun
Toyohara, Takafumi
Suzuki, Takehiro
Mishima, Eikan
Akiyama, Yasutoshi
Ogata, Yoshiaki
Suzuki, Chitose
Hayashi, Hironori
Kodama, Eiichi N.
Hayashi, Ken-ichiro
Itoi, Eiji
Aoki, Masashi
Kure, Shigeo
Abe, Takaaki
Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title_full Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title_fullStr Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title_full_unstemmed Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title_short Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
title_sort mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug ma-5
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710105/
https://www.ncbi.nlm.nih.gov/pubmed/33264289
http://dx.doi.org/10.1371/journal.pone.0231064
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