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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7710105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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