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dc.contributor.authorRhein, VFen
dc.contributor.authorCarroll, Josephen
dc.contributor.authorHe, Jayen
dc.contributor.authorDing, Sen
dc.contributor.authorFearnley, Ianen
dc.contributor.authorWalker, Johnen
dc.date.accessioned2017-08-11T10:50:09Z
dc.date.available2017-08-11T10:50:09Z
dc.date.issued2014-08-29en
dc.identifier.issn0021-9258
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266264
dc.description.abstractIn mammalian mitochondria, protein methylation is a relatively uncommon post-transcriptional modification, and the extent of the mitochondrial protein methylome, the modifying methyltransferases, and their substrates have been little studied. As shown here, the β-subunit of the electron transfer flavoprotein (ETF) is one such methylated protein. The ETF is a heterodimer of α- and β-subunits. Lysine residues 199 and 202 of mature ETFβ are almost completely trimethylated in bovine heart mitochondria, whereas ETFα is not methylated. The enzyme responsible for the modifications was identified as methyltransferase-like protein 20 (METTL20). In human 143B cells, the methylation of ETFβ is less extensive and is diminished further by suppression of METTL20. Tagged METTL20 expressed in HEK293T cells specifically associates with the ETF and promotes the trimethylation of ETFβ lysine residues 199 and 202. ETF serves as a mobile electron carrier linking dehydrogenases involved in fatty acid oxidation and one-carbon metabolism to the membrane-associated ubiquinone pool. The methylated residues in ETFβ are immediately adjacent to a protein loop that recognizes and binds to the dehydrogenases. Suppression of trimethylation of ETFβ in mouse C2C12 cells oxidizing palmitate as an energy source reduced the consumption of oxygen by the cells. These experiments suggest that the oxidation of fatty acids in mitochondria and the passage of electrons via the ETF may be controlled by modulating the protein-protein interactions between the reduced dehydrogenases and the β-subunit of the ETF by trimethylation of lysine residues. METTL20 is the first lysine methyltransferase to be found to be associated with mitochondria.
dc.description.sponsorshipThis work was supported by the Medical Research Council (MRC), UK.
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBioenergeticsen
dc.subjectElectron Transfer Flavoproteinen
dc.subjectElectron Transport System (ETS)en
dc.subjectFlavoproteinen
dc.subjectMethyltransferaseen
dc.subjectMitochondrial Metabolismen
dc.subjectProtein Methylationen
dc.subjectTrimethyllysineen
dc.subjectAmino Acid Sequenceen
dc.subjectBase Sequenceen
dc.subjectCell Line, Tumoren
dc.subjectChromatography, Affinityen
dc.subjectDNA Primersen
dc.subjectElectron Transporten
dc.subjectFlavoproteinsen
dc.subjectHumansen
dc.subjectLysineen
dc.subjectMass Spectrometryen
dc.subjectMethylationen
dc.subjectMethyltransferasesen
dc.subjectMitochondriaen
dc.subjectMolecular Sequence Dataen
dc.titleHuman METTL20 methylates lysine residues adjacent to the recognition loop of the electron transfer flavoprotein in mitochondria.en
dc.typeArticle
prism.endingPage24651
prism.issueIdentifier35en
prism.publicationDate2014en
prism.publicationNameJournal of Biological Chemistryen
prism.startingPage24640
prism.volume289en
dc.identifier.doi10.17863/CAM.9994
dcterms.dateAccepted2014-06-30en
rioxxterms.versionofrecord10.1074/jbc.M114.580464en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2014-08-29en
dc.contributor.orcidWalker, John [0000-0001-7929-2162]
dc.identifier.eissn1083-351X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_U105663148)
cam.issuedOnline2014-07-14en


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