Low dose resveratrol ameliorates mitochondrial respiratory dysfunction and enhances cellular reprogramming
Low dose resveratrol ameliorates mitochondrial respiratory dysfunction and enhances cellular reprogramming
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DOI：
10.1016/j.mito.2016.12.006
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发表时间：
2017-05-01
期刊：
影响因子：
4.4
通讯作者：
Goto, Yu-ichi
中科院分区：
文献类型：
--
作者：
Mizuguchi, Yuki;Hatakeyama, Hideyuki;Goto, Yu-ichi
线粒体疾病与多种临床表现相关，甚至在携带异质性线粒体DNA（mtDNA）突变的患者中也是如此，这可能是因为组织和器官水平上突变mtDNA比例的变化。虽然一些病例报告和临床试验已经评估了各种类型的药物和补充剂治疗线粒体疾病的有效性，但目前还没有治愈这些疾病的方法。在这项研究中，我们首次证明了低剂量白藜芦醇（RSV）改善了携带同质mtDNA突变的患者来源的成纤维细胞的线粒体呼吸功能障碍。此外，低剂量RSV还促进患者来源的成纤维细胞有效地细胞重编程为诱导多能干细胞，部分原因是细胞活力改善。我们的研究结果突出了RSV作为治疗线粒体疾病的新的治疗药物候选者的潜力。(C)2017年Elsevier BV和线粒体研究学会。All rights reserved.
Mitochondrial disease is associated with a wide variety of clinical presentations, even among patients carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, probably because of variations in mutant mtDNA proportions at the tissue and organ levels. Although several case reports and clinical trials have assessed the effectiveness of various types of drugs and supplements for the treatment of mitochondrial diseases, there are currently no cures for these conditions. In this study, we demonstrated for the first time that low dose resveratrol (RSV) ameliorated mitochondrial respiratory dysfunction in patient-derived fibroblasts carrying homoplasmic mtDNA mutations. Furthermore, low dose RSV also facilitated efficient cellular reprogramming of the patient-derived fibroblasts into induced pluripotent stem cells, partly due to improved cellular viability. Our results highlight the potential of RSV as a new therapeutic drug candidate for the treatment of mitochondrial diseases. (C) 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.