In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 12 ( 2020-12-2), p. e0231064-
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0231064
DOI:
10.1371/journal.pone.0231064.g001
DOI:
10.1371/journal.pone.0231064.g002
DOI:
10.1371/journal.pone.0231064.g003
DOI:
10.1371/journal.pone.0231064.g004
DOI:
10.1371/journal.pone.0231064.g005
DOI:
10.1371/journal.pone.0231064.g006
DOI:
10.1371/journal.pone.0231064.t001
DOI:
10.1371/journal.pone.0231064.s001
DOI:
10.1371/journal.pone.0231064.s002
DOI:
10.1371/journal.pone.0231064.s003
DOI:
10.1371/journal.pone.0231064.s004
DOI:
10.1371/journal.pone.0231064.s005
DOI:
10.1371/journal.pone.0231064.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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