Show simple item record

dc.contributor.authorWright, John J
dc.contributor.authorBiner, Olivier
dc.contributor.authorChung, Injae
dc.contributor.authorBurger, Nils
dc.contributor.authorBridges, Hannah R
dc.contributor.authorHirst, Judy
dc.date.accessioned2022-05-09T11:04:38Z
dc.date.available2022-05-09T11:04:38Z
dc.date.issued2022-04-20
dc.identifier.issn0002-7863
dc.identifier.other35380814
dc.identifier.otherPMC9026280
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336909
dc.description.abstractRespiratory complex I is an essential metabolic enzyme that uses the energy from NADH oxidation and ubiquinone reduction to translocate protons across an energy transducing membrane and generate the proton motive force for ATP synthesis. Under specific conditions, complex I can also catalyze the reverse reaction, Δp-linked oxidation of ubiquinol to reduce NAD+ (or O2), known as reverse electron transfer (RET). Oxidative damage by reactive oxygen species generated during RET underpins ischemia reperfusion injury, but as RET relies on several converging metabolic pathways, little is known about its mechanism or regulation. Here, we demonstrate Δp-linked RET through complex I in a synthetic proteoliposome system for the first time, enabling complete kinetic characterization of RET catalysis. We further establish the capability of our system by showing how RET in the mammalian enzyme is regulated by the active-deactive transition and by evaluating RET by complex I from several species in which direct assessment has not been otherwise possible. We thus provide new insights into the reversibility of complex I catalysis, an important but little understood mechanistic and physiological feature.
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 7503056
dc.sourceessn: 1520-5126
dc.subjectAnimals
dc.subjectMammals
dc.subjectElectron Transport Complex I
dc.subjectNAD
dc.subjectElectron Transport
dc.subjectOxidation-Reduction
dc.subjectCatalysis
dc.subjectElectrons
dc.titleReverse Electron Transfer by Respiratory Complex I Catalyzed in a Modular Proteoliposome System.
dc.typeArticle
dc.date.updated2022-05-09T11:04:38Z
prism.endingPage6801
prism.issueIdentifier15
prism.publicationNameJ Am Chem Soc
prism.startingPage6791
prism.volume144
dc.identifier.doi10.17863/CAM.84328
rioxxterms.versionofrecord10.1021/jacs.2c00274
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidWright, John J [0000-0001-8987-4449]
dc.contributor.orcidBiner, Olivier [0000-0001-6935-2475]
dc.contributor.orcidChung, Injae [0000-0002-2902-4677]
dc.contributor.orcidBurger, Nils [0000-0003-3227-8894]
dc.contributor.orcidBridges, Hannah R [0000-0001-6890-6050]
dc.contributor.orcidHirst, Judy [0000-0001-8667-6797]
dc.identifier.eissn1520-5126
pubs.funder-project-idMedical Research Council (MC_UU_00015/7)
pubs.funder-project-idMRC (MC_UU_00015/2)
cam.issuedOnline2022-04-05


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International