Statin-induced mitochondrial toxicity: an insight from yeast

Sylvie Callegari, Stuart Andrews, Ross McKinnon, Miguel de Barros Lopes

    Research output: Contribution to conferenceAbstract

    Abstract

    Statins are among the most highly prescribed drugs in the world.
    However, many patients experience side-effects, commonly affecting
    skeletal muscle. The mitochondria are one of the molecular targets of
    statins, and these drugs have been known to uncover otherwise silent
    mitochondrial mutations. Despite the statin-mitochondrial link, the
    possibility that polymorphisms in mitochondrial proteins may influence
    an individual’s response to statin toxicity had not been investigated.
    Based on yeast genetic studies, the yeast MEF2 gene, encoding
    a mitochondrial ribosome recycling factor, was discovered to be a
    significant mediator of atorvastatin toxicity in yeast cells. The yeast
    Mef2 protein is essential for respiratory function and has a human
    homolog, the EF-G2mt protein, which contains a number of amino
    acid variants arising from Single Nucleotide Polymorphisms (SNPs) in
    the EF-G2mt gene. Many of these variants are conserved in the yeast
    Mef2 protein and so to investigate their effect on cell statin toxicity, five
    of the mutations were constructed in the yeast MEF2 gene. Despite
    the absence of an obvious respiratory defect, three of the mutants
    revealed an increase in cell statin sensitivity phenotype and further
    analysis uncovered a decreased respiratory capacity. To establish the
    significance of the EF-G2mt gene in the statin response of human cell
    lines, siRNA knockdown technology was used to transiently decrease
    expression of the EF-G2mt g ene i n t he H epG2 a nd R D c ell l ines.
    Results show an almost 20% increase in statin sensitivity amongst cells
    with decreased EF-G2mt gene expression.
    Original languageEnglish
    Pages62-62
    Number of pages1
    Publication statusPublished - 2012
    EventComBio2012 - Adelaide Convention Centre, Adelaide, Australia
    Duration: 23 Sep 201227 Sep 2012
    https://www.asbmb.org.au/meetings/combio/ (Information about the conference)

    Conference

    ConferenceComBio2012
    CountryAustralia
    CityAdelaide
    Period23/09/1227/09/12
    Other'ComBio (“combined biosciences”) is ASBMB’s national biennial conference run in conjunction with other societies. Programs feature world renowned international speakers alongside a range of high calibre Australian presenters. Meeting themes cover a wide range of topics to appeal across a broad spectrum of interests to biochemists and molecular biologists. ComBio is a fantastic networking opportunity, through both scientific and social events.
    Internet address

    Keywords

    • Statins
    • mitochondria
    • yeast

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  • Cite this

    Callegari, S., Andrews, S., McKinnon, R., & de Barros Lopes, M. (2012). Statin-induced mitochondrial toxicity: an insight from yeast. 62-62. Abstract from ComBio2012, Adelaide, Australia.