title: A third isoform of cytochrome c oxidase subunit VIII is present in mammals.
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.
authors.affiliation: Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Schmidt
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007900:Lemur / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; D021122:Protein Subunits; C477826:COX8C protein, human; C477827:Cox8c protein, rat; D003576:Electron Transport Complex IV