Unbound MEDLINE

The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis.

Abstract

We have previously reported a heteroplasmic mtDNA mutation (T1095C) in the 12SrRNA gene of an Italian family with features of maternally-inherited parkinsonism, antibiotic-mediated deafness and peripheral neuropathy. In the present study, we demonstrate that a transmitochondrial cybrid line derived from the proband of this family shows selective depletion of mitochondrial glutathione and decreases in the activity of complex II/III. Moreover, when exposed to an aminoglycoside antibiotic these cells responded with a ten-fold increase in the number of apoptotic cells compared to controls. These results support a pathogenic role for the T1095C mutation and indicate that the mutation increases the risk for aminoglycoside-induced toxicity.

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  • Publisher Full Text
  • Authors

    Muyderman H, Sims NR, Tanaka M, Fuku N, Raghupathi R, Thyagarajan D

    Source

    Mitochondrion 12:4 2012 Jul pg 465-71

    MeSH

    Anti-Bacterial Agents
    Apoptosis
    Cell Line
    DNA, Mitochondrial
    Genes, rRNA
    Gentamicins
    Humans
    Italy
    Mitochondria
    Point Mutation
    RNA, Ribosomal

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22735573