We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production. In the first patient, complex I activity, mitochondrial respiration, and mitochondrial ATP production were decreased in the mutation-high clones compared with the mutation-undetectable clones, and mitochondrial membrane potential was decreased in a mutation-high clone compared with a mutation-undetectable clone. In the second patient, complex I activity was decreased in one mutation-high clone compared with the other clones. The other parameters showed no differences in any clones. In addition, the complex I activity and mitochondrial respiration of the mutation-undetectable clones from both patients were located in the range of those of iPS cells from healthy subjects. The present study suggests that the mitochondrial function of the mutation-undetectable iPS cell clones obtained from two patients with the A3243G mutation is comparable to the control iPS cells.

中文翻译：

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由于A3243G突变而导致的人诱导的线粒体糖尿病患者多能干细胞中线粒体功能的分析。

我们先前在两名来自线粒体A3243G突变的不同家族的糖尿病患者中建立了人类诱导的多能干（iPS）细胞，并在这两名患者中分离出了突变水平均未检测到的同基因iPS细胞克隆。在本研究中，我们通过四种方法分析了每位患者中两个无法检测到的突变和两个突变高的克隆的线粒体功能，以评估复合体I活性，线粒体膜电位，线粒体呼吸作用和线粒体ATP的产生。在第一个患者中，高突变的克隆与无法检测到突变的克隆相比，复合物I活性，线粒体呼吸作用和线粒体ATP产量降低，高突变的克隆与不可突变的克隆相比，线粒体膜电位降低了。在第二例患者中，一个突变高的克隆中的复杂I活性比其他克隆降低。其他参数在任何克隆中均无差异。另外，来自两个患者的突变检测不到的克隆的复杂I活性和线粒体呼吸都位于健康受试者的iPS细胞的范围内。本研究表明，从两名患有A3243G突变的患者获得的无法检测到突变的iPS细胞克隆的线粒体功能与对照iPS细胞相当。另外，来自两个患者的突变检测不到的克隆的复杂I活性和线粒体呼吸都位于健康受试者的iPS细胞的范围内。本研究表明，从两名患有A3243G突变的患者获得的无法检测到突变的iPS细胞克隆的线粒体功能与对照iPS细胞相当。另外，来自两个患者的突变检测不到的克隆的复杂I活性和线粒体呼吸都位于健康受试者的iPS细胞的范围内。本研究表明，从两名患有A3243G突变的患者获得的无法检测到突变的iPS细胞克隆的线粒体功能与对照iPS细胞相当。