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dc.contributor.authorRodriguez-Enriquez, Sara
dc.contributor.authorHernandez-Esquivel, Luz
dc.contributor.authorMarin-Hernandez, Alvaro
dc.contributor.authorDong, Lan-Feng
dc.contributor.authorAkporiaye, Emmanuel T
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorRalph, Stephen J
dc.contributor.authorMoreno-Sanchez, Rafael
dc.date.accessioned2017-05-03T14:14:58Z
dc.date.available2017-05-03T14:14:58Z
dc.date.issued2012
dc.date.modified2013-06-04T03:31:32Z
dc.identifier.issn0005-2728
dc.identifier.doi10.1016/j.bbabio.2012.05.005
dc.identifier.urihttp://hdl.handle.net/10072/47607
dc.description.abstractThe effects of a-tocopheryl succinate (a-TOS), a-tocopheryl acetyl ether (a-TEA) and triphenylphosphonium-tagged vitamin E succinate (mitochondrially targeted vitamin E succinate; MitoVES) on energy-related mitochondrial functions were determined in mitochondria isolated from AS-30D hepatoma and rat liver, bovine heart sub-mitochondrial particles (SMPs), and in rodent and human carcinoma cell lines and rat hepatocytes. In isolated mitochondria, MitoVES stimulated basal respiration and ATP hydrolysis, but inhibited net state 3 (ADP-stimulated) respiration and Ca(2+) uptake, by collapsing the membrane potential at low doses (1-10卩. Uncoupled mitochondrial respiration and basal respiration of SMPs were inhibited by the three drugs at concentrations at least one order of magnitude higher and with different efficacy: MitoVES>a-TEA>a-TOS. At high doses (>10卩, the respiratory complex II (CII) was the most sensitive MitoVES target. Acting as an uncoupler at low doses, this agent stimulated total O(2) uptake, collapsed ??(m), inhibited oxidative phosphorylation and induced ATP depletion in rodent and human cancer cells more potently than in normal rat hepatocytes. These findings revealed that in situ tumor mitochondria are preferred targets of the drug, indicating its clinical relevance.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_US
dc.publisherElsevier
dc.publisher.placeNetherlands
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1597
dc.relation.ispartofpageto1607
dc.relation.ispartofissue9
dc.relation.ispartofjournalBiochimica et Biophysica Acta - Bioenergetics
dc.relation.ispartofvolume1817
dc.rights.retentionY
dc.subject.fieldofresearchMolecular Targets
dc.subject.fieldofresearchPhysical Chemistry (incl. Structural)
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode111207
dc.subject.fieldofresearchcode0306
dc.subject.fieldofresearchcode0601
dc.titleMolecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri
gro.griffith.authorRalph, Stephen J.
gro.griffith.authorDong, Lan-feng


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