scholarly journals Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

2016 ◽  
Vol 130 (19) ◽  
pp. 1741-1751 ◽  
Author(s):  
Marc Catalán-García ◽  
Glòria Garrabou ◽  
Constanza Morén ◽  
Mariona Guitart-Mampel ◽  
Adriana Hernando ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Phosphorylation ◽  
Inclusion Body ◽  
Blood Cells ◽  
Fusion Proteins ◽  
Inclusion Body Myositis ◽  
Mitochondrial Dynamics ◽  
Sporadic Inclusion Body Myositis ◽  
Oxphos System

In this study, we describe the role of mitochondria in sIBM, demonstrating that deregulated mitochondrial dynamics correlates with altered mtDNA stability and that the OXPHOS system is also impaired in both muscle and blood cells of these patients.

Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: A study of 56 patients

1996 ◽  
Vol 39 (6) ◽  
pp. 789-795 ◽  
Author(s):  
F. M. Santorelli ◽  
M. Sciacco ◽  
K. Tanji ◽  
S. Shanske ◽  
T. H. Vu ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Dna Deletions ◽  
Sporadic Inclusion Body Myositis

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

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0231064
Author(s):  
Yoshitsugu Oikawa ◽  
Rumiko Izumi ◽  
Masashi Koide ◽  
Yoshihiro Hagiwara ◽  
Makoto Kanzaki ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Mitochondrial Dynamics ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Mitochondrial Morphology ◽  
Atp Production ◽  
Bioenergetic Analysis ◽  
Sporadic Inclusion Body Myositis

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.

The role of p62/SQSTM1 in sporadic inclusion body myositis

2017 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Satoshi Nakano ◽  
Mitsuaki Oki ◽  
Hirofumi Kusaka
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Sporadic Inclusion Body Myositis

scholarly journals Mitochondrial DNA depletion in sporadic inclusion body myositis

2019 ◽  
Vol 29 (3) ◽  
pp. 242-246 ◽  
Author(s):  
Padmanabh S. Bhatt ◽  
Charalampos Tzoulis ◽  
Novin Balafkan ◽  
Hrvoje Miletic ◽  
Gia Tuong Thi Tran ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Mitochondrial Dna Depletion ◽  
Sporadic Inclusion Body Myositis

scholarly journals Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3255
Author(s):  
Manuela Piazzi ◽  
Alberto Bavelloni ◽  
Vittoria Cenni ◽  
Irene Faenza ◽  
William L. Blalock
Keyword(s):  
Inclusion Body ◽  
Inclusion Bodies ◽  
Inclusion Body Myositis ◽  
Glycogen Synthase ◽  
Slowing Down ◽  
Age Related ◽  
Degenerative Disorders ◽  
Sporadic Inclusion Body Myositis ◽  
Degenerative Disorder

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.

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

2020 ◽  
Author(s):  
Yoshitsugu Oikawa ◽  
Rumiko Izumi ◽  
Masashi Koide ◽  
Yoshihiro Hagiwara ◽  
Makoto Kanzaki ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Mitochondrial Dynamics ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Mitochondrial Morphology ◽  
Atp Production ◽  
Bioenergetic Analysis ◽  
Sporadic Inclusion Body Myositis

AbstractSporadic 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.

scholarly journals Sporadic Inclusion Body Myositis: An Acquired Mitochondrial Disease with Extras

Biomolecules ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 15 ◽  
Author(s):  
Boel De Paepe
Keyword(s):  
Inclusion Body ◽  
Mitochondrial Disease ◽  
Inclusion Body Myositis ◽  
Late Onset ◽  
Mitochondrial Dynamics ◽  
Muscle Disorders ◽  
Morphological Alterations ◽  
Mitochondrial Alterations ◽  
Sporadic Inclusion Body Myositis ◽  
Mitochondrial Abnormality

The sporadic form of inclusion body myositis (IBM) is the most common late-onset myopathy. Its complex pathogenesis includes degenerative, inflammatory and mitochondrial aspects. However, which of those mechanisms are cause and which effect, as well as their interrelations, remain partly obscured to this day. In this review the nature of the mitochondrial dysregulation in IBM muscle is explored and comparison is made with other muscle disorders. Mitochondrial alterations in IBM are evidenced by histological and serum biomarkers. Muscular mitochondrial dynamics is disturbed, with deregulated organelle fusion leading to subsequent morphological alterations and muscle displays abnormal mitophagy. The tissue increases mitochondrial content in an attempt to compensate dysfunction, yet mitochondrial DNA (mtDNA) alterations and mild mtDNA depletion are also present. Oxidative phosphorylation defects have repeatedly been shown, most notably a reduction in complex IV activities and levels of mitokines and regulatory RNAs are perturbed. Based on the cumulating evidence of mitochondrial abnormality as a disease contributor, it is therefore warranted to regard IBM as a mitochondrial disease, offering a feasible therapeutic target to be developed for this yet untreatable condition.

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