title: Cytochrome c oxidase assembly in primates is sensitive to small evolutionary variations in amino acid sequence.
abstract: 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 approximately 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.
authors.affiliation: Department of Neurology, University of Miami, School of Medicine, Miami, FL 33136, USA.
authors.forename: A
authors.initials: A
authors.lastname: Barrientos
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Dey
authors.forename: J
authors.initials: J
authors.lastname: Wienberg
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002467:Cell Nucleus / Q000235:genetics*; D002642:Chick Embryo; D003576:Electron Transport Complex IV / Q000235:genetics*; D019143:Evolution, Molecular; D006071:Gorilla gorilla / Q000235:genetics; D000882:Haplorhini / Q000235:genetics*; D015186:Hominidae / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics*; D010085:Oxidative Phosphorylation; D011148:Pongo pygmaeus / Q000235:genetics; D013045:Species Specificity
chemical_list: D003576:Electron Transport Complex IV