title: Mitochondrial abnormalities in myofibrillar myopathies.
abstract: Histological mitochondrial changes are generally found to be associated with late onset myofibrillar myopathies (MFMs). How these changes contribute to the pathogenesis of MFMs is unknown. Mitochondrial changes, including COX-deficient fibers (n = 8), biochemical activities of respiratory chain complexes (n = 7), and multiple mtDNA deletions by long-range PCR (n = 9) were examined in patients with genetically confirmed MFMs [MYOT (n = 2), DES (n = 1), ZASP (n = 2), FLNC (n = 4)] and compared with age and sex matched normal controls (n = 27) and patients with a mitochondrial disorder with multiple mtDNA deletions due to nuclear genetic defects (n = 8). In 2 MFM patients, micro dissected fibers were analyzed for multiple mtDNA deletions by nested long-range PCR. The COX-deficient fibers only partly corresponded with fibers containing myofibrillar accumulations. In total, there was no difference in the percentage of COX-deficient fibers in MFM patients and normal controls. However, the percentage of COX-deficient fibers was significantly higher in 3 MFM patients. Two MFM patients but none of the controls had multiple mtDNA deletions. Nested long-range PCR detected multiple mtDNA deletions only in COX-deficient fibers. Citrate synthase activities in MFM patients were 1.5-fold increased by compared to those in controls, suggesting initiation of mitochondrial alterations. However, it is unclear whether this is a direct consequence of MFM pathology. *both authors contributed equally to the manuscript.
authors.forename: Pushpa R
authors.initials: PR
authors.lastname: Joshi
authors.forename: Anja
authors.initials: A
authors.lastname: Hauburger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kley
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Ilka
authors.initials: I
authors.lastname: Schneider
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
authors.forename: Frank
authors.initials: F
authors.lastname: Hanisch
mesh_terms: D000328:Adult; D000368:Aged; D064211:Connectin / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008840:Microfilament Proteins; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000473:pathology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D020914:Myopathies, Structural, Congenital / Q000473:pathology; D016133:Polymerase Chain Reaction
chemical_list: D064211:Connectin; D004272:DNA, Mitochondrial; C577290:MYOT protein, human; D008840:Microfilament Proteins; D004247:DNA; D003576:Electron Transport Complex IV