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

Authors :
Catalán-García M
Garrabou G
Morén C
Guitart-Mampel M
Hernando A
Díaz-Ramos À
González-Casacuberta I
Juárez DL
Bañó M
Enrich-Bengoa J
Emperador S
Milisenda JC
Moreno P
Tobías E
Zorzano A
Montoya J
Cardellach F
Grau JM
Source :
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2016 Oct 01; Vol. 130 (19), pp. 1741-51. Date of Electronic Publication: 2016 Jul 13.
Publication Year :
2016

Abstract

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age- and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients.<br /> (© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Details

Language :
English
ISSN :
1470-8736
Volume :
130
Issue :
19
Database :
MEDLINE
Journal :
Clinical science (London, England : 1979)
Publication Type :
Academic Journal
Accession number :
27413019
Full Text :
https://doi.org/10.1042/CS20160080