Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation.
Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation.
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由于A3243G突变而导致线粒体糖尿病患者的人类诱导的多能干细胞中线粒体功能的分析。
DOI：
10.1038/s41598-018-19264-7
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Nakao K
中科院分区：
文献类型：
--
作者：
Matsubara M;Kanda H;Imamura H;Inoue M;Noguchi M;Hosoda K;Kakizuka A;Nakao K
我们之前在两名来自不同家族的线粒体A3243G突变的糖尿病患者中建立了人类诱导多能干细胞（iPS），并分离出在两名患者中检测不到或高水平突变的等基因iPS细胞克隆。在本研究中，我们通过四种方法分析了每个患者的两个突变不可检测克隆和两个突变高克隆的线粒体功能，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。在第一位患者中，与突变检测不到的克隆相比，高突变克隆的复合体I活性、线粒体呼吸和线粒体ATP产生降低，高突变克隆的线粒体膜电位与突变检测不到的克隆相比降低。在第二例患者中，与其他克隆相比，一个高突变克隆的复合体I活性降低。其他参数在各无性系间无差异。此外，来自两名患者的突变检测不到的克隆的复合物I活性和线粒体呼吸位于健康受试者的iPS细胞的范围内。目前的研究表明，从两名A3243G突变患者获得的突变不可检测的iPS细胞克隆的线粒体功能与对照iPS细胞相当。
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.
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影响因子：
64.8
作者：
GOTO, Y;NONAKA, I;HORAI, S
通讯作者：
HORAI, S
与成年线粒体疾病有关的核和线粒体DNA突变的患病率。
影响因子：
11.2
作者：
Gorman GS;Schaefer AM;Ng Y;Gomez N;Blakely EL;Alston CL;Feeney C;Horvath R;Yu-Wai-Man P;Chinnery PF;Taylor RW;Turnbull DM;McFarland R
通讯作者：
McFarland R
影响因子：
2.6
作者：
Kodaira, Masaki;Hatakeyama, Hideyuki;Yuasa, Shinsuke;Seki, Tomohisa;Egashira, Toru;Tohyama, Shugo;Kuroda, Yusuke;Tanaka, Atsushi;Okata, Shinichiro;Hashimoto, Hisayuki;Kusumoto, Dai;Kunitomi, Akira;Takei, Makoto;Kashimura, Shin;Suzuki, Tomoyuki;Yozu, Gakuto;Shimojima, Masaya;Motoda, Chikaaki;Hayashiji, Nozomi;Saito, Yuki;Goto, Yu-ichi;Fukuda, Keiichi
通讯作者：
Fukuda, Keiichi
影响因子：
29
作者：
Folmes CD;Nelson TJ;Martinez-Fernandez A;Arrell DK;Lindor JZ;Dzeja PP;Ikeda Y;Perez-Terzic C;Terzic A
通讯作者：
Terzic A
影响因子：
5.2
作者：
Folmes, Clifford D. L.;Martinez-Fernandez, Almudena;Perales-Clemente, Ester;Li, Xing;Mcdonald, Amber;Oglesbee, Devin;Hrstka, Sybil C.;Perez-Terzic, Carmen;Terzic, Andre;Nelson, Timothy J.
通讯作者：
Nelson, Timothy J.