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Evolution of the oxygen sensitivity of cytochrome c oxidase subunit 4.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2015 Feb 15; Vol. 308 (4), pp. R305-20. Date of Electronic Publication: 2014 Dec 17. - Publication Year :
- 2015
-
Abstract
- Vertebrates possess two paralogs of cytochrome c oxidase (COX) subunit 4: a ubiquitous COX4-1 and a hypoxia-linked COX4-2. Mammalian COX4-2 is thought to have a role in relation to fine-tuning metabolism in low oxygen levels, conferred through both structural differences in the subunit protein structure and regulatory differences in the gene. We sought to elucidate the pervasiveness of this feature across vertebrates. The ratio of COX4-2/4-1 mRNA is generally low in mammals, but this ratio was higher in fish and reptiles, particularly turtles. The COX4-2 gene appeared unresponsive to low oxygen in nonmammalian models (zebrafish, goldfish, tilapia, anoles, and turtles) and fish cell lines. Reporter genes constructed from the amphibian and reptile homologues of the mammalian oxygen-responsive elements and hypoxia-responsive elements did not respond to low oxygen. Unlike the rodent ortholog, the promoter of goldfish COX4-2 did not respond to hypoxia or anoxia. The protein sequences of the COX4-2 peptide showed that the disulfide bridge seen in human and rodent orthologs would be precluded in other mammalian lineages and lower vertebrates, all of which lack the requisite pair of cysteines. The coordinating ligands of the ATP-binding site are largely conserved across mammals and reptiles, but in Xenopus and fish, sequence variations may disrupt the ability of the protein to bind ATP at this site. Collectively, these results suggest that many of the genetic and structural features of COX4-2 that impart responsiveness and benefits in hypoxia may be restricted to the Euarchontoglires lineage that includes primates, lagomorphs, and rodents.<br /> (Copyright © 2015 the American Physiological Society.)
- Subjects :
- Adaptation, Physiological
Adenosine Triphosphate metabolism
Amino Acid Sequence
Animals
Binding Sites
Cell Hypoxia
Cell Line
Conserved Sequence
Cysteine
Disulfides metabolism
Electron Transport Complex IV chemistry
Electron Transport Complex IV genetics
Fish Proteins chemistry
Fish Proteins genetics
Gene Expression Regulation, Enzymologic
Humans
Isoenzymes
Mice
Molecular Sequence Data
Phylogeny
Promoter Regions, Genetic
RNA, Messenger metabolism
Reptilian Proteins chemistry
Reptilian Proteins genetics
Species Specificity
Transcription, Genetic
Transcriptional Activation
Transfection
Electron Transport Complex IV metabolism
Evolution, Molecular
Fish Proteins metabolism
Oxygen metabolism
Reptilian Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 308
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 25519729
- Full Text :
- https://doi.org/10.1152/ajpregu.00281.2014