Discipline of Medical Biochemistry and Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
Mitochondrion. 2012 Jul;12(4):465-71. doi: 10.1016/j.mito.2012.06.006. Epub 2012 Jun 24.
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.
我们之前报道了一个意大利家族中与母系遗传帕金森病、抗生素介导的耳聋和周围神经病相关的线粒体 DNA 突变（T1095C），该突变位于 12SrRNA 基因中。在本研究中，我们证明了源自该家族先证者的传递线粒体细胞系表现出线粒体谷胱甘肽的选择性耗竭和复合物 II/III 活性降低。此外，当这些细胞暴露于氨基糖苷类抗生素时，与对照组相比，凋亡细胞的数量增加了十倍。这些结果支持 T1095C 突变的致病性作用，并表明该突变增加了氨基糖苷类药物诱导毒性的风险。
