|ZFIN ID: ZDB-PUB-141219-10|
Evolution of the oxygen sensitivity of cytochrome c oxidase subunit 4
Kocha, K.M., Reilly, K., Porplycia, D.S., McDonald, J., Snider, T., Moyes, C.D.
|Source:||American journal of physiology. Regulatory, integrative and comparative physiology 308(4): R305-20 (Journal)|
|Registered Authors:||Kocha, Katrinka|
|PubMed:||25519729 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.|
Kocha, K.M., Reilly, K., Porplycia, D.S., McDonald, J., Snider, T., Moyes, C.D. (2015) Evolution of the oxygen sensitivity of cytochrome c oxidase subunit 4. American journal of physiology. Regulatory, integrative and comparative physiology. 308(4):R305-20.
ABSTRACTVertebrates possess two paralogs of cytochrome oxidase subunit 4: a ubiquitous COX4-1 and a hypoxia-linked COX4-2. Mammalian COX4-2 is thought to have a special role in fine-tuning metabolism in relation to oxygen levels, conferred through both structural differences in the subunit protein structure and regulatory differences in the gene. The ratio of COX4-2 / 4-1 mRNA are 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 non-mammalian models (zebrafish, goldfish, tilapia, anoles, 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 the 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.