bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–06–29
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. The binding sites of carbon dioxide, nitrous oxide, and xenon reveal a putative exhaust channel for bovine cytochrome c oxidase.
  2. Investigating the cardiorespiratory fitness gene COX7A2L in cardiomyocytes: Viability and mitochondrial function.
  1. J Biol Chem. 2025 Jun 19. pii: S0021-9258(25)02245-8. [Epub ahead of print] 110395
    The binding sites of carbon dioxide, nitrous oxide, and xenon reveal a putative exhaust channel for bovine cytochrome c oxidase.
    Kazumasa Muramoto, Tomohiro Ide, Kyoko Shinzawa-Itoh.
      Cytochrome c oxidase (CcO) catalyzes oxygen (O2) reduction at the heme a3-CuB site in the transmembrane region of the enzyme. It has been proposed that the hydrophobic channel that connects the transmembrane surface of subunit III through subunit I to the heme a3-CuB site is the O2 transfer pathway. Gas molecules other than O2, including carbon dioxide (CO2) generated in the TCA cycle, should also enter the hydrophobic channel, but it is not clear how these molecules are expelled from CcO. We analyzed the crystal structures of CO2-, nitrous oxide (N2O)-, and Xe-bound bovine CcO in the oxidized and reduced states at resolutions of 1.75-1.85 Å. Binding of Xe in the channel of subunit I near the interface with subunit III supported the proposed O2 transfer pathway. CO2, N2O, and another Xe were all bound to a common site near the branching point of another hydrophobic channel that branched from the O2 transport channel. Additional Xe atoms were bound in the second channel leading up to the molecular surface on the intermembrane space side, suggesting that under physiological conditions, CO2 that has entered the O2 pathway could be passively expelled through this channel. This channel consists of subunits I and nuclear DNA-coded subunit VIIc, suggesting that the addition of subunit VIIc in the process of molecular evolution of mitochondrial CcO has made the CO2 exhaust pathway.
    Keywords:  X-ray crystallography; Xe; carbon dioxide; cytochrome c oxidase; nitrous oxide; oxygen transport; protein structure
    DOI:  https://doi.org/10.1016/j.jbc.2025.110395
  2. PLoS One. 2025 ;20(6): e0326249
    Investigating the cardiorespiratory fitness gene COX7A2L in cardiomyocytes: Viability and mitochondrial function.
    Ada Nilsen Nordeidet, Gurdeep S A Marwarha, Øystein Røsand, Victoria Johansen, Karin Garten, Morten A Høydal, Mette Langaas, Anja Bye.
      Low cardiorespiratory fitness (CRF) is a well-established risk factor for cardiovascular disease (CVD) and all-cause mortality. Since CRF is largely genetically determined, understanding the genetic influences on CRF might reveal the protective mechanisms of high CRF. One gene found to be associated with CRF is COX7A2L. COX7A2L is a mitochondrial supercomplex assembly factor, but its role in cellular metabolism remains a topic of discussion. We hypothesized that COX7A2L could play a role in cellular respiration in cardiomyocytes, affecting cardiac function and CRF. To determine the effect of COX7A2L on cardiomyocyte function, we overexpressed and knocked down COX7A2L in human AC16 cardiomyocytes and performed MTT assays and Seahorse XF Cell Mito Stress Tests to assess cell viability and mitochondrial function. For the mitochondrial function measurements, we stimulated the cells with isoproterenol to investigate if the effect of altering COX7A2L levels would be larger under simulated increased energy demand. Overexpression and knockdown were validated using sandwich ELISA. Our findings showed that altering COX7A2L expression in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function. Further research is necessary to determine whether COX7A2L influences cardiomyocyte function and CRF.
    DOI:  https://doi.org/10.1371/journal.pone.0326249
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