ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2015
Evolution of the oxygen sensitivity of cytochrome c oxidase subunit 4.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 31 citations in OpenAlex.
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- Transcriptome analysis of five-toed jerboa organs reveals high-altitude adaptation mechanisms.BMC genomics · 2025Article
- Tumor Necrosis Factor Receptor-2 Signals Clear-Cell Renal Carcinoma Proliferation via Phosphorylated 4E Binding Protein-1 and Mitochondrial Gene Translation.The American journal of pathology · 2024Article
- The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.ESC heart failure · 2024Article
- Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight.International journal of molecular sciences · 2022Review
- Hydrogen-rich water ameliorates neuropathological impairments in a mouse model of Alzheimer's disease through reducing neuroinflammation and modulating intestinal microbiota.Neural regeneration research · 2022Article
- AMPK and the Need to Breathe and Feed: What's the Matter with Oxygen?International journal of molecular sciences · 2020Review
- Long-term HIF-1α transcriptional activation is essential for heat-acclimation-mediated cross tolerance: mitochondrial target genes.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- Subfunctionalization of COX4 paralogs in fish.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- Tissue- and Condition-Specific Isoforms of Mammalian CytochromeOxidative medicine and cellular longevity · 2017Review
- The emerging role of AMPK in the regulation of breathing and oxygen supply.The Biochemical journal · 2016Review
- Utilizing comparative models in biomedical research.Comparative biochemistry and physiology. Part B, Biochemistry & molecular biologyReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.