The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy

Neuromuscul Disord. 2002 Nov;12(9):858-64. doi: 10.1016/s0960-8966(02)00047-0.


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.

Publication types

  • Case Reports
  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Blotting, Southern
  • Cytochrome-c Oxidase Deficiency*
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Mitochondrial Diseases / enzymology*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / pathology
  • Mitochondrial Myopathies / enzymology*
  • Mitochondrial Myopathies / genetics
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology


  • DNA, Mitochondrial
  • Electron Transport Complex IV