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Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.

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cam.issuedOnline2018-06-21
dc.contributor.authorFedor, Justin G
dc.contributor.authorHirst, Judy
dc.contributor.orcidHirst, Judy [0000-0001-8667-6797]
dc.date.accessioned2018-09-27T14:09:16Z
dc.date.available2018-09-27T14:09:16Z
dc.date.issued2018-09-04
dc.description.abstractMitochondrial respiratory supercomplexes, comprising complexes I, III, and IV, are the minimal functional units of the electron transport chain. Assembling the individual complexes into supercomplexes may stabilize them, provide greater spatiotemporal control of respiration, or, controversially, confer kinetic advantages through the sequestration of local quinone and cytochrome c pools (substrate channeling). Here, we have incorporated an alternative quinol oxidase (AOX) into mammalian heart mitochondrial membranes to introduce a competing pathway for quinol oxidation and test for channeling. AOX substantially increases the rate of NADH oxidation by O2 without affecting the membrane integrity, the supercomplexes, or NADH-linked oxidative phosphorylation. Therefore, the quinol generated in supercomplexes by complex I is reoxidized more rapidly outside the supercomplex by AOX than inside the supercomplex by complex III. Our results demonstrate that quinone and quinol diffuse freely in and out of supercomplexes: substrate channeling does not occur and is not required to support respiration.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.30136
dc.identifier.eissn1932-7420
dc.identifier.issn1550-4131
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282772
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.cmet.2018.05.024
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectalternative oxidase
dc.subjectchanneling
dc.subjectmitochondria
dc.subjectoxidative phosphorylation
dc.subjectrespirasome
dc.subjectsupercomplex
dc.subjectubiquinone
dc.subjectAnimals
dc.subjectBenzoquinones
dc.subjectBiocatalysis
dc.subjectCattle
dc.subjectCell Respiration
dc.subjectElectron Transport Complex I
dc.subjectElectron Transport Complex III
dc.subjectElectron Transport Complex IV
dc.subjectFemale
dc.subjectKinetics
dc.subjectMale
dc.subjectMitochondria, Heart
dc.subjectMitochondrial Membranes
dc.subjectOxidation-Reduction
dc.subjectOxidative Phosphorylation
dc.subjectOxidoreductases
dc.titleMitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.
dc.typeArticle
dcterms.dateAccepted2018-05-24
prism.endingPage531.e4
prism.issueIdentifier3
prism.publicationDate2018
prism.publicationNameCell Metab
prism.startingPage525
prism.volume28
pubs.funder-project-idMedical Research Council (MC_U105663141)
pubs.funder-project-idMRC (MC_UP_1002/1)
pubs.funder-project-idMRC (MC_UU_00015/2)
pubs.funder-project-idMedical Research Council (MC_UP_1002/1)
pubs.funder-project-idMedical Research Council (MC_UU_00015/7)
rioxxterms.licenseref.startdate2018-09
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.cmet.2018.05.024

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