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- Title
Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5.
- Authors
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
- Abstract
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.
- Subjects
INCLUSION body myositis; MYOSITIS; ETIOLOGY of diseases; CELL morphology; MYOBLASTS; OXIDATIVE stress
- Publication
PLoS ONE, 2020, Vol 15, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0231064