Open AccessMitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5
Author(s) -
Yoshitsugu Oikawa,
Rumiko Izumi,
Masashi Koide,
Yoshihiro Hagiwara,
Makoto Kanzaki,
Naoki Suzuki,
Kôichi Kikuchi,
Tomohiro Matsuhashi,
Yukako Akiyama,
M. Ichijo,
Shun Watanabe,
Takafumi Toyohara,
Takehiro Suzuki,
Eikan Mishima,
Yasutoshi Akiyama,
Yoshiaki Ogata,
Chitose Suzuki,
Hironori Hayashi,
Eiichi N. Kodama,
Kenichiro Hayashi,
Eiji Itoi,
Masashi Akiyama,
Shigeo Kure,
Takaaki Abe
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0231064
Subject(s) - mitochondrial fission , mitochondrion , mitochondrial fusion , myocyte , oxidative stress , biology , mfn2 , mitochondrial myopathy , bioenergetics , microbiology and biotechnology , mitochondrial dna , medicine , endocrinology , biochemistry , gene
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.