Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions

Nat Genet. 1992 Aug;1(5):359-67. doi: 10.1038/ng0892-359.


Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially-deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild-type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Southern
  • Cytochrome-c Oxidase Deficiency
  • DNA Probes
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kearns-Sayre Syndrome / enzymology
  • Kearns-Sayre Syndrome / genetics*
  • Kearns-Sayre Syndrome / pathology
  • MELAS Syndrome / genetics
  • MERRF Syndrome / genetics
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / pathology*
  • Oculomotor Muscles / enzymology
  • Oculomotor Muscles / pathology*
  • Polymerase Chain Reaction / methods
  • RNA / analysis
  • RNA / genetics
  • RNA, Mitochondrial
  • Sequence Deletion*
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism


  • DNA Probes
  • DNA, Mitochondrial
  • RNA, Mitochondrial
  • RNA
  • Succinate Dehydrogenase
  • Electron Transport Complex IV