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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 ASEP 0383182 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular 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 Title Biochimica Et Biophysica Acta-Bioenergetics. - : Elsevier - ISSN 0005-2728
Roč. 1817, č. 9 (2012), s. 1597-1607Number of pages 21 s. Language eng - English Country NL - Netherlands Keywords Mitochondria ; respiratory complex II ; vitamin E analogs Subject RIV CE - Biochemistry R&D Projects GAP301/10/1937 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000306536400008 DOI 10.1016/j.bbabio.2012.05.005 Annotation The 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2013
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