title: The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy.
abstract: Heteroplasmic mitochondrial DNA mutations often cause a skeletal myopathy associated with a mosaic distribution of cytochrome c oxidase-deficient muscle fibres. The function of an individual muscle fibre is dependent upon the metabolic activity throughout its length, but little is known about the length of cytochrome c oxidase-deficient segments in human skeletal muscle in patients with mitochondrial disease. We studied cytochrome c oxidase activity by serial section analysis of quadriceps muscle from two patients. We observed a striking variation in the length of the cytochrome c oxidase-negative segments. The shortest segments were 10 microm long, and the longest segment was the entire length of the larger biopsy (> or =1.2 mm). The lengths of the cytochrome c oxidase-negative segments were generally shorter in the less severely affected biopsy, and we frequently observed non-contiguous segments of cytochrome c oxidase deficiency within the same muscle fibre. The findings have important implications for our understanding of the pathogenesis and progression of mitochondrial DNA myopathy.
authors.affiliation: Department of Neurology, University of Newcastle upon Tyne, The Medical School, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Elson
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015139:Blotting, Southern; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV