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dc.contributor.authorDong, Lan-fengen_US
dc.contributor.authorKelly, Paulineen_US
dc.contributor.authorDyason, Jeffreyen_US
dc.contributor.authorWang, Xiufangen_US
dc.contributor.authorProchazka, Len_US
dc.contributor.authorWitting, PKen_US
dc.contributor.authorLambrechts, Ruthen_US
dc.contributor.authorSwettenham, Een_US
dc.contributor.authorValis, Ken_US
dc.contributor.authorZobalova, Renataen_US
dc.contributor.authorTuranek, Jen_US
dc.contributor.authorSpitz, DRen_US
dc.contributor.authorDomann, FEen_US
dc.contributor.authorScheffler, IEen_US
dc.contributor.authorRalph, Stephenen_US
dc.contributor.authorNeuzil, Jirien_US
dc.contributor.editorDr. E Premkumar Reddy, Dr. John Jenkinsen_US
dc.date.accessioned2017-04-24T14:53:01Z
dc.date.available2017-04-24T14:53:01Z
dc.date.issued2008en_US
dc.date.modified2010-03-03T06:41:13Z
dc.identifier.issn09509232en_US
dc.identifier.doi10.1038/onc.2008.69en_AU
dc.identifier.urihttp://hdl.handle.net/10072/23242
dc.description.abstracta-Tocopheryl succinate (a-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of a-TOS has not been identified. Here, we show that a-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (QP and QD, respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of a-TOS compared to that of UbQ for the QP and QD sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of a-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to a-TOS. We propose that a-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. 頲008 Macmillan Publishers Limited All rights reserved.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent135893 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherMacmillan Publishers Limiteden_US
dc.publisher.placeUnited Kingdomen_US
dc.publisher.urihttp://www.nature.com/onc/index.htmlen_AU
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom4324en_US
dc.relation.ispartofpageto4335en_US
dc.relation.ispartofissue31en_US
dc.relation.ispartofjournalOncogeneen_US
dc.relation.ispartofvolume27en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classifieden_US
dc.subject.fieldofresearchcode060199en_US
dc.titleα-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex IIen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightCopyright 2008 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.en_AU
gro.date.issued2008
gro.hasfulltextFull Text


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