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Mitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis

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    SYSNO ASEP0444249
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis
    Author(s) Truksa, Jaroslav (BTO-N) RID, ORCID
    Dong, L.F. (AU)
    Rohlena, Jakub (BTO-N) RID, ORCID
    Stursa, J. (AU)
    Vondrusová, Magdaléna (BTO-N) RID
    Goodwin, J. (AU)
    Nguyen, M. (AU)
    Klučková, Katarína (BTO-N) RID
    Rychtarčíková, Zuzana (BTO-N)
    Lettlová, Sandra (BTO-N)
    Spáčilová, Jana (BTO-N)
    Stapelberg, M. (AU)
    Zoratti, M. (IT)
    Neužil, Jiří (BTO-N) RID
    Source TitleAntioxidants & Redox Signaling. - : Mary Ann Liebert - ISSN 1523-0864
    Roč. 22, č. 11 (2015), s. 883-900
    Number of pages18 s.
    Languageeng - English
    CountryUS - United States
    KeywordsALPHA-TOCOPHERYL SUCCINATE ; ELECTRON-TRANSPORT CHAIN ; RESPIRATORY COMPLEX-II
    Subject RIVEB - Genetics ; Molecular Biology
    R&D ProjectsGAP301/10/1937 GA ČR - Czech Science Foundation (CSF)
    KAN200520703 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
    GAP305/12/1708 GA ČR - Czech Science Foundation (CSF)
    GAP301/12/1851 GA ČR - Czech Science Foundation (CSF)
    ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportBTO-N - RVO:86652036
    CEZAV0Z50520701 - BTO-N (2007-2013)
    UT WOS000351944100001
    DOI10.1089/ars.2013.5594
    AnnotationAims: To assess the effect of mitochondrially targeted vitamin E (VE) analogs on mitochondrial function and biogenesis. Results: Mitochondrially targeted vitamin E succinate (MitoVES) is an efficient inducer of apoptosis in cancer cells. Here, we show that unlike its untargeted counterpart alpha-tocopheryl succinate, MitoVES suppresses proliferation of cancer cells at sub-apoptotic doses by way of affecting the mitochondrial DNA (mtDNA) transcripts. We found that MitoVES strongly suppresses the level of the displacement loop transcript followed by those of mtDNA genes coding for subunits of mitochondrial complexes. This process is coupled to the inhibition of mitochondrial respiration, dissipation of the mitochondrial membrane potential, and generation of reactive oxygen species. In addition, exposure of cancer cells to MitoVES led to decreased expression of TFAM and diminished mitochondrial biogenesis. The inhibition of mitochondrial transcription was replicated in vivo in a mouse model of HER2(high) breast cancer, where MitoVES lowered the level of mtDNA transcripts in cancer cells but not in normal tissue. Innovation: Our data show that mitochondrially targeted VE analogs represent a novel class of mitocans that not only induce apoptosis at higher concentrations but also block proliferation and suppress normal mitochondrial function and transcription at low, non-apoptogenic doses. Conclusions: Our data indicate a novel, selective anti-cancer activity of compounds that act by targeting mitochondria of cancer cells, inducing significant alterations in mitochondrial function associated with transcription of mtDNA-coded genes. These changes subsequently result in the arrest of cell proliferation
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2016
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