The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis
2012
Muyderman, Hakan | Sims, Neil R. | Tanaka, Masashi | Fuku, Noriyuki | Raghupathi, Ravinarayan | Thyagarajan, Dominic
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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