TY - JOUR
T1 - The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis
AU - Muyderman, Hakan
AU - Sims, Neil
AU - Tanaka, Masashi
AU - Fuku, Noriyuki
AU - Raghupathi, Ravinarayan
AU - Thyagarajan, Dominic
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/22735573
U2 - 10.1016/j.mito.2012.06.006
DO - 10.1016/j.mito.2012.06.006
M3 - Article
SN - 1567-7249
VL - 12
SP - 465
EP - 471
JO - Mitochondrion
JF - Mitochondrion
IS - 4
ER -