The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis

Hakan Muyderman, Neil Sims, Masashi Tanaka, Noriyuki Fuku, RaviNarayan Raghupathi, Dominic Thyagarajan

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    6 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)465-471
    Number of pages7
    JournalMitochondrion
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - Jul 2012

    Keywords

    • 12SrRNA
    • Aminoglycosides
    • Apoptosis
    • Mitochondrial DNA
    • Mitochondrial parkinsonism
    • T1095C

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