A third isoform of cytochrome c oxidase subunit VIII is present in mammals

Gene. 2003 Jul 17:312:95-102. doi: 10.1016/s0378-1119(03)00604-8.

Abstract

The terminal enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (COX), contains three mitochondrial and ten nuclear encoded subunits in mammals. Three of the nuclear subunits (VIa, VIIa, and VIII) have muscle and non-muscle-specific isoforms, subunit IV contains a lung-specific isoform, and subunit VIb contains a testes-specific isoform. For subunit VIII, the smallest nuclear encoded COX polypeptide, we have now found a third gene (COX 8-3), which has been identified in human, lemur, rat, and mouse, suggesting that it is present in a broad range of Eutherian mammals. Sequence similarity and gene structure support the homology of COX8-3 to the other subunit VIII isoforms, indicating that all three are the product of gene duplications. COX VIII-3 protein is mitochondrially-targeted, as shown by a fluorescent COX VIII3/DsRed fusion protein. Both the mitochondrial targeting and its sequence conservation suggest that COXVIII-3 functions as part of the COX holoenzyme and could have a tissue-specific role, as is the case for the other two isoforms. Questions remain about where COX8-3 is predominantly expressed. However, detection of full-length cDNAs, lower levels of sequence divergence at the first and second codon positions compared to the third, and a conserved gene structure indicate that COX VIII-3 is an expressed gene whose origin dates to at least 91 million years ago.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Electron Transport Complex IV / genetics*
  • Evolution, Molecular
  • Gene Expression Regulation, Enzymologic
  • HeLa Cells
  • Humans
  • Isoenzymes / genetics
  • Lemur / genetics*
  • Male
  • Mitochondria / enzymology
  • Molecular Sequence Data
  • Phylogeny
  • Protein Subunits / genetics
  • Rats
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid

Substances

  • DNA, Complementary
  • Isoenzymes
  • Protein Subunits
  • COX8C protein, human
  • Cox8c protein, rat
  • Electron Transport Complex IV

Associated data

  • GENBANK/AY161004
  • GENBANK/AY161005
  • GENBANK/AY161006