title: Functional relevance of mitochondrial abnormalities in sporadic inclusion body myositis.
abstract: Cytochrome c oxidase (COX)-deficient fibers and multiple mitochondrial DNA (mtDNA) deletions are frequent findings in sporadic inclusion body myositis (s-IBM). However, the functional impact of these defects is not known. We investigated oxygen desaturation during exercise using the forearm exercise test, accumulation of lactate during exercise using a cycle ergometry test and mitochondrial changes (COX-deficient fibers, biochemical activities of respiratory chain complexes, multiple mtDNA deletions by long-range polymerase chain reaction) in 10 patients with s-IBM and compared the findings with age and sex-matched normal and diseased controls (without mitochondrial disorders) as well as patients with mitochondrial disorder due to nuclear gene defects resulting in multiple mtDNA deletions (MITO group). The mean age of the s-IBM patients was 68.2 ± 5.7 years (range: 56-75). Patients with s-IBM had statistically significantly reduced oxygen desaturation (ΔsO2) during the handgrip exercise (p<0.05) and elevated peak serum lactate levels during cycle ergometry compared to normal controls (p<0.05). The percentage of COX-deficient fibers in s-IBM and MITO patients was significantly increased compared to normal controls (p<0.01). Five out of nine s-IBM patients had multiple mtDNA deletions. Thirty-three percent of s-IBM patients showed an increased citrate synthase content and decreased activities of complex IV (COX). The biochemical pattern of respiratory chain complexes in patients with s-IBM and MITO was similar. Histopathological analysis showed similar changes in s-IBM and MITO due to nuclear gene defects. Functional tests reflecting mitochondrial impairment suggest a contribution of mitochondrial defects to disease-related symptoms such as fatigue and exertion-induced symptoms.
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. Electronic address: pushpa.joshi@medizin.uni-halle.de.
authors.forename: Pushpa Raj
authors.initials: PR
authors.lastname: Joshi
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Vetterke
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hauburger
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Tacik
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany; Institute of Cell Biology and Neurobiology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hanisch
mesh_terms: D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D016552:Ergometry; D005221:Fatigue / Q000209:etiology / Q000503:physiopathology; D005260:Female; D018737:Hand Strength; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D018979:Myositis, Inclusion Body / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D019344:Lactic Acid; D003576:Electron Transport Complex IV
keywords: Cycle ergometry test; Forearm exercise test; Mitochondria; Multiple deletions; Oxygen consumption; Sporadic inclusion body myositis