Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial diseases MELAS and LHON

FEBS Lett. 1998 Aug 14;433(1-2):93-7. doi: 10.1016/s0014-5793(98)00891-6.


Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Poracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e ratio and lower deltapsi), but had similar CO activity. These results indicate that both substitutions (F263L > A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.

Publication types

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

MeSH terms

  • Ascorbic Acid / pharmacology
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Gene Deletion
  • Gene Expression
  • Humans
  • Kinetics
  • MELAS Syndrome / enzymology
  • MELAS Syndrome / genetics*
  • Onium Compounds / metabolism
  • Optic Atrophies, Hereditary / enzymology
  • Optic Atrophies, Hereditary / genetics*
  • Organophosphorus Compounds / metabolism
  • Paracoccus denitrificans / enzymology
  • Paracoccus denitrificans / genetics
  • Paracoccus denitrificans / growth & development
  • Proton Pumps / metabolism
  • Tetramethylphenylenediamine / pharmacology


  • DNA, Mitochondrial
  • Onium Compounds
  • Organophosphorus Compounds
  • Proton Pumps
  • Electron Transport Complex IV
  • Tetramethylphenylenediamine
  • Ascorbic Acid
  • tetraphenylphosphonium