Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly. Mitochondrial abnormalities at histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease etiology. We measured in muscle and peripheral blood mononuclear cells (PBMC) from 30 sIBM patients and 38 age and gender-paired controls: mitochondrial DNA (mtDNA) deletions, mtDNA and mtRNA amount, mitochondrial protein synthesis, mitochondrial respiratory complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (MFN2 and OPA1 levels). mtDNA depletion was present in muscle from sIBM patients and PBMC showed deregulated expression of OXPHOS mitochondrial proteins. Mitochondrial respiratory chain complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics was affected in muscle. mtDNA depletion 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 homeostasis and muscle function in these patients.
- Inclusion body myositis
- OXPHOS system
- mtDNA depletion
- ©2016 The Author(s)
This is an Accepted Manuscript; not the final Version of Record. Archiving permitted only in line with the archiving policy of Portland Press Limited. All other rights reserved.