Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy

Hum Mol Genet. 1994 Jan;3(1):13-9. doi: 10.1093/hmg/3.1.13.


We studied the cellular distribution of both deleted (delta) and wild-type (wt) mitochondrial DNAs (mtDNAs) in 'normal' and respiration-deficient muscle fibers from four patients with mitochondrial myopathy. PCR-based methods were used to quantitate both relative and absolute amounts of delta- and wt-mtDNAs in microdissected fiber segments. Although delta-mtDNAs were present in normal fibers (31% +/- 26), their percentages were much higher in affected fibers (95% +/- 2). Absolute levels of delta-mtDNA were also increased in affected fibers, whereas levels of wt-mtDNA were significantly reduced in these fibers. These results indicate that a threshold ratio of delta-/wt-mtDNA must be achieved before an impairment of respiration is observed in muscle. Moreover, the marked reduction in wt-mtDNA observed in affected fibers suggests that absolute amounts of mtDNA may play a role in the pathogenesis of mitochondrial myopathies.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blotting, Southern
  • Cytochrome-c Oxidase Deficiency
  • DNA Primers
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / analysis
  • Electron Transport Complex IV / genetics*
  • Female
  • Humans
  • Kearns-Sayre Syndrome / genetics
  • MELAS Syndrome / genetics
  • MERRF Syndrome / genetics
  • Male
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Muscles / metabolism*
  • Muscles / pathology
  • Oxygen Consumption
  • Polymerase Chain Reaction / methods
  • Restriction Mapping
  • Sequence Deletion*
  • Succinate Dehydrogenase / analysis


  • DNA Primers
  • DNA, Mitochondrial
  • Succinate Dehydrogenase
  • Electron Transport Complex IV