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Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex
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SYSNO ASEP 0361293 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex Author(s) Dong, L.F. (NZ)
Jameson, V.J.A. (NZ)
Tilly, D. (AU)
Černý, Jiří (BTO-N) RID, ORCID
Mahdavian, E. (US)
Marin-Hernandez, A. (MX)
Hernandez-Esquivel, L. (MX)
Rodriguez-Enriquez, S. (MX)
Štursa, Jan (UOCHB-X)
Witting, P.K. (AU)
Stantic, B. (AU)
Rohlena, Jakub (BTO-N) RID, ORCID
Truksa, Jaroslav (BTO-N) RID, ORCID
Klučková, Katarína (BTO-N) RID
Dyason, J.C. (AU)
Ledvina, Miroslav (UOCHB-X) RID
Salvatore, B.A. (US)
Moreno-Sanchez, R. (MX)
Coster, M. (AU)
Ralph, S.J. (NZ)
Smith, A.J. (NZ)
Neužil, Jiří (BTO-N) RIDNumber of authors 22 Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 286, č. 5 (2011), s. 3717-3728Number of pages 12 s. Language eng - English Country US - United States Keywords Apoptosis induction ; proximal ubiquinone-binding site of mitochondrial complex II ; reactive oxygen species Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA204/08/0811 GA ČR - Czech Science Foundation (CSF) GAP301/10/1937 GA ČR - Czech Science Foundation (CSF) IAA500520702 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) KAN200520703 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) KJB500970904 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) CEZ AV0Z50520701 - BTO-N (2007-2013) AV0Z4055905 - UOCHB-X UT WOS 000286653200054 DOI 10.1074/jbc.M110.186643 Annotation Mitochondrially targeted vitamin E succinate (MitoVES) has enhanced pro-apoptotic and anti-cancer activities. It caused apoptosis and generation of ROS in CII-proficient malignant cells but not their CII-dysfunctional counterparts. It inhibited SDH activity of CII with IC50 of 80 mu M and electron transfer from CII to CIII with IC50 of 1.5 mu M. Molecular modeling predicted its succinyl group anchored into the proximal CII ubiquinone (UbQ)-binding site and reduced interaction energies for its serially shorter phytyl chain homologs correlated with their lower effects on apoptosis induction, ROS generation, and SDH activity. Mutation of the UbQ-binding Ser(68) within the proximal site of the CII SDHC subunit suppressed both ROS generation and apoptosis induction by it. We propose that mitochondrial targeting of VES with an 11-carbon chain localizes the agent into an ideal position across the interface of the mitochondrial inner membrane and matrix, optimizing its anti-cancer effect Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2013
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