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dc.contributor.authorYin, Zhan
dc.contributor.authorBurger, Nils
dc.contributor.authorKula-Alwar, Duvaraka
dc.contributor.authorAksentijević, Dunja
dc.contributor.authorBridges, Hannah R.
dc.contributor.authorPrag, Hiran A.
dc.contributor.authorGrba, Daniel N.
dc.contributor.authorViscomi, Carlo
dc.contributor.authorJames, Andrew M.
dc.contributor.authorMottahedin, Amin
dc.contributor.authorKrieg, Thomas
dc.contributor.authorMurphy, Michael P.
dc.contributor.authorHirst, Judy
dc.date.accessioned2021-01-29T17:22:00Z
dc.date.available2021-01-29T17:22:00Z
dc.date.issued2021-01-29
dc.date.submitted2020-09-22
dc.identifier.others41467-021-20942-w
dc.identifier.other20942
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316863
dc.descriptionFunder: RCUK | MRC | Medical Research Foundation; doi: https://doi.org/10.13039/501100009187
dc.description.abstractAbstract: Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia–reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the “deactive” state, usually formed only after prolonged inactivity. Despite its tendency to adopt the “deactive” state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/45/56
dc.subject/631/45/535/1258/1259
dc.subject/631/57/1464
dc.subject/9
dc.subject/101
dc.subject/101/28
dc.subjectarticle
dc.titleStructural basis for a complex I mutation that blocks pathological ROS production
dc.typeArticle
dc.date.updated2021-01-29T17:21:59Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
dc.identifier.doi10.17863/CAM.63976
dcterms.dateAccepted2020-12-23
rioxxterms.versionofrecord10.1038/s41467-021-20942-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidYin, Zhan [0000-0002-3846-0147]
dc.contributor.orcidBurger, Nils [0000-0003-3227-8894]
dc.contributor.orcidAksentijević, Dunja [0000-0002-8480-6727]
dc.contributor.orcidBridges, Hannah R. [0000-0001-6890-6050]
dc.contributor.orcidPrag, Hiran A. [0000-0002-4753-8567]
dc.contributor.orcidGrba, Daniel N. [0000-0003-2915-951X]
dc.contributor.orcidMottahedin, Amin [0000-0002-3677-2198]
dc.contributor.orcidKrieg, Thomas [0000-0002-5192-580X]
dc.contributor.orcidMurphy, Michael P. [0000-0003-1115-9618]
dc.contributor.orcidHirst, Judy [0000-0001-8667-6797]
dc.identifier.eissn2041-1723


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