Mitochondrial dysfunction in juvenile and adult dermatomyositis

Abstract

Introduction Previous studies have shown perifascicular regions in dermatomyositis with mitochondrial abnormalities affecting complex IV also known as cytochrome c oxidase (COX) in the respiratory chain. The aim of this study was to further investigate the mitochondrial dysfunction that is present in dermatomyositis by investigating complex I-V in the respiratory chain within skeletal muscle areas diagnosed with dermatomyositis, which show a manifest COX deficiency. Method Muscle biopsy specimens from the muscle biobank at the Sahlgrenska University Hospital in Gothenburg were used. Ten cases (four juvenile and six adults) were selected based on a diagnosis of dermatomyositis and presence of marked deficiency of cytochrome c oxidase in the perifascicular region. Two age matched controls and one disease control were chosen for a total of 13 patients in this study. Sections, with 8μm thickness, were incubated through enzyme histochemistry with cytochrome c oxidase COX (CIV), succinate dehydrogenase SDH (CII) and COX/SDH or through immunohistochemistry with antibodies for the five different complexes (complex I-V) in the respiratory chain. Results COX deficiency was profound in the perifascicular regions. Immunohistochemical analysis of complex I and IV subunits showed markedly reduced expression in perifascicular regions corresponding to the same areas showing low COX enzymatic activity. No deficiency of complex II, III and V were found. Conclusion This study has provided new evidence that the mitochondrial dysfunction in dermatomyositis is due to an absence of complex I and IV in the respiratory chain. Further research on the mitochondrial dysfunction of complex I and IV in dermatomyositis may lead to better understanding of the disease and through that create better treatment and management.