Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Sci Rep. 2018 Jan 17;8(1):949. doi: 10.1038/s41598-018-19264-7.
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.
我们之前在两名来自不同家庭的糖尿病患者中建立了带有线粒体 A3243G 突变的人诱导多能干细胞（iPS），并在两名患者中分别分离出突变低水平和高水平的同基因 iPS 细胞克隆。在本研究中，我们通过四种方法分析了两名患者的两个突变低水平和两个突变高水平克隆的线粒体功能，以评估复合物 I 活性、线粒体膜电位、线粒体呼吸和线粒体 ATP 产生。在第一例患者中，与突变低水平克隆相比，突变高水平克隆的复合物 I 活性、线粒体呼吸和线粒体 ATP 产生降低，而与突变低水平克隆相比，一个突变高水平克隆的线粒体膜电位降低。在第二例患者中，与其他克隆相比，一个突变高水平克隆的复合物 I 活性降低。其他参数在任何克隆中均无差异。此外，两名患者的突变低水平克隆的复合物 I 活性和线粒体呼吸位于健康供体 iPS 细胞的范围内。本研究表明，来自 A3243G 突变患者的突变低水平 iPS 细胞克隆的线粒体功能与对照 iPS 细胞相当。
