Isoforms of mammalian cytochrome c oxidase: correlation with human cytochrome c oxidase deficiency

Pediatr Res. 1990 Nov;28(5):529-35. doi: 10.1203/00006450-199011000-00024.


We have reviewed the structure, function, and biogenesis of mammalian cytochrome c oxidase, examined the tissue-specific expression of isoforms of cytochrome c oxidase subunits in different mammals, and attempted to correlate the data with our knowledge of cytochrome c oxidase deficiency, illustrated by one particular patient. Cytochrome c oxidase was isolated from bovine tissues, and individual subunits examined by SDS-PAGE, N-terminal peptide sequencing, and antibody binding. Isoforms of subunits VIa, VIIa, and VIII were identified, manifesting one pattern of expression in heart and skeletal muscle, and another in liver, kidney, and brain. In rat heart and liver, only one form of subunit VIIa was identified. Northern analysis of bovine and rat tissues suggested that the tissue-specific expression of subunits VIa and VIII is regulated transcriptionally in liver, kidney, and brain, and posttranscriptionally in heart and skeletal muscle. In humans, antibody binding documented isoforms of subunits VIa and VIIa, with the pattern of expression in heart and skeletal muscle differing from that in liver, kidney, and brain; our data suggested that both isoforms of subunit VIa may be expressed in human heart. In a patient with cytochrome c oxidase deficiency, the clinical, morphologic, and biochemical manifestations were much more severe in heart than in skeletal muscle. Antibody binding suggested partial assembly of the enzyme in heart. These and other data suggest considerably more variability in the tissue-specific expression of isoforms of cytochrome c oxidase subunits than previously recognized.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cardiomyopathies / enzymology
  • Cardiomyopathies / etiology
  • Cattle
  • Cytochrome-c Oxidase Deficiency*
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / genetics
  • Female
  • Humans
  • Infant, Newborn
  • Molecular Sequence Data
  • Oxygen Consumption
  • Rats
  • Species Specificity
  • Tissue Distribution


  • Electron Transport Complex IV