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A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria

Maréchal, A; Xu, J-Y; Genko, N; Hartley, AM; Haraux, F; Meunier, B; Rich, PR; (2020) A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria. Proceedings of the National Academy of Sciences 10.1073/pnas.2001572117. (In press). Green open access

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Abstract

Mitochondria metabolize almost all the oxygen that we consume, reducing it to water by cytochrome c oxidase (CcO). CcO maximizes energy capture into the protonmotive force by pumping protons across the mitochondrial inner membrane. Forty years after the H+/e- stoichiometry was established, a consensus has yet to be reached on the route taken by pumped protons to traverse CcO's hydrophobic core and on whether bacterial and mitochondrial CcOs operate via the same coupling mechanism. To resolve this, we exploited the unique amenability to mitochondrial DNA mutagenesis of the yeast Saccharomyces cerevisiae to introduce single point mutations in the hydrophilic pathways of CcO to test function. From adenosine diphosphate to oxygen ratio measurements on preparations of intact mitochondria, we definitely established that the D-channel, and not the H-channel, is the proton pump of the yeast mitochondrial enzyme, supporting an identical coupling mechanism in all forms of the enzyme.

Type: Article
Title: A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2001572117
Publisher version: https://doi.org/10.1073/pnas.2001572117
Language: English
Additional information: © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Keywords: ADP/O ratio, H/e stoichiometry, cytochrome c oxidase, mitochondria, proton pumping
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10095019
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