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Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue

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    SYSNO ASEP0383182
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMolecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue
    Author(s) Rodriguez-Enriquez, S. (MX)
    Hernandez-Esquivel, L. (MX)
    Marin-Hernandez, A. (MX)
    Dong, L.-F. (AU)
    Akporiaye, E. (US)
    Neužil, Jiří (BTO-N) RID
    Ralph, S.J. (AU)
    Moreno-Sanchez, R. (MX)
    Source TitleBiochimica Et Biophysica Acta-Bioenergetics. - : Elsevier - ISSN 0005-2728
    Roč. 1817, č. 9 (2012), s. 1597-1607
    Number of pages21 s.
    Languageeng - English
    CountryNL - Netherlands
    KeywordsMitochondria ; respiratory complex II ; vitamin E analogs
    Subject RIVCE - Biochemistry
    R&D ProjectsGAP301/10/1937 GA ČR - Czech Science Foundation (CSF)
    CEZAV0Z50520701 - BTO-N (2007-2013)
    UT WOS000306536400008
    DOI10.1016/j.bbabio.2012.05.005
    AnnotationThe effects of alpha-tocopheryl succinate (alpha-TOS), alpha-tocopheryl acetyl ether (alpha-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 Ca2+ uptake, by collapsing the membrane potential at low doses (1-10 mu M). 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> alpha-TEA>alpha-TOS. At high doses (>10 mu M), 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 Delta Psi(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. (C) 2012 Elsevier B.V. All rights reserved.
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2013
Number of the records: 1