Cytochrome c oxidase assembly in primates is sensitive to small evolutionary variations in amino acid sequence

Antoni Barrientos, Stefan Müller, Runu Dey, Johannes Wienberg, Carlos T. Moraes

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Respiring mitochondria require many interactions between nuclear and mitochondrial genomes. Although mitochondrial DNA (mtDNA) from the gorilla and the chimpanzee are able to restore oxidative phosphorylation in a human cell, mtDNAs from more distant primate species are functionally incompatible with human nuclear genes. Using microcell-mediated chromosome and mitochondria transfer, we introduced and maintained a functional orangutan mtDNA in a human nuclear background. However, partial oxidative phosphorylation function was restored only in the presence of most orangutan chromosomes, suggesting that human oxidative phosphorylation-related nuclear-coded genes are not able to replace many orangutan ones. The respiratory capacity of these hybrids was decreased by 65%-80%, and cytochrome c oxidase (COX) activity was decreased by 85%-95%. The function of other respiratory complexes was not significantly altered. The translation of mtDNA-coded COX subunits was normal, but their steady-state levels were ~10% of normal ones. Nuclear-coded COX subunits were loosely associated with mitochondrial membranes, a characteristic of COX assembly-defective mutants. Our results suggest that many human nuclear-coded genes not only cannot replace the orangutan counterparts, but also exert a specific interference at the level of COX assembly. This cellular model underscores the precision of COX assembly in mammals and sheds light on the nature of nuclear-mtDNA coevolutionary constraints.

Original languageEnglish (US)
Pages (from-to)1508-1519
Number of pages12
JournalMolecular biology and evolution
Issue number10
StatePublished - 2000


  • COX
  • Evolution
  • Hybrids
  • Mitochondria
  • mtDNA

ASJC Scopus subject areas

  • Genetics
  • Biochemistry
  • Genetics(clinical)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Ecology, Evolution, Behavior and Systematics
  • Agricultural and Biological Sciences (miscellaneous)
  • Molecular Biology


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