Hsu Yi-Chao, Chen Chien-Tsun, Wei Yau-Huei
Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, 252, Taiwan.
Department of Medicine, Mackay Medical College, New Taipei City, 252, Taiwan.
Biochim Biophys Acta. 2016 Apr;1860(4):686-93. doi: 10.1016/j.bbagen.2016.01.009. Epub 2016 Jan 15.
Nuclear reprogramming with pluripotency factors enables somatic cells to gain the properties of embryonic stem cells. Mitochondrial resetting and metabolic reprogramming are suggested to be key early events in the induction of human skin fibroblasts to induced pluripotent stem cells (iPSCs).
We review recent advances in the study of the molecular basis for mitochondrial resetting and metabolic reprogramming in the regulation of the formation of iPSCs. In particular, the recent progress in using iPSCs for mitochondrial disease modeling was discussed.
iPSCs rely on glycolysis rather than oxidative phosphorylation as a major supply of energy. Mitochondrial resetting and metabolic reprogramming thus play crucial roles in the process of generation of iPSCs from somatic cells.
Neurons, myocytes, and cardiomyocytes are cells containing abundant mitochondria in the human body, which can be differentiated from iPSCs or trans-differentiated from fibroblasts. Generating these cells from iPSCs derived from skin fibroblasts of patients with mitochondrial diseases or by trans-differentiation with cell-specific transcription factors will provide valuable insights into the role of mitochondrial DNA heteroplasmy in mitochondrial disease modeling and serves as a novel platform for screening of drugs to treat patients with mitochondrial diseases.
利用多能性因子进行核重编程可使体细胞获得胚胎干细胞的特性。线粒体重置和代谢重编程被认为是诱导人皮肤成纤维细胞成为诱导多能干细胞（iPSC）过程中的关键早期事件。
我们综述了iPSC形成调控中线粒体重置和代谢重编程分子基础研究的最新进展。特别讨论了利用iPSC进行线粒体疾病建模的最新进展。
iPSC依赖糖酵解而非氧化磷酸化作为主要能量供应。因此，线粒体重置和代谢重编程在体细胞生成iPSC的过程中起着关键作用。
神经元、肌细胞和心肌细胞是人体中含有丰富线粒体的细胞，它们可从iPSC分化而来或由成纤维细胞转分化而来。从线粒体疾病患者的皮肤成纤维细胞衍生的iPSC或通过细胞特异性转录因子转分化来生成这些细胞，将为线粒体DNA异质性在线粒体疾病建模中的作用提供有价值的见解，并作为筛选治疗线粒体疾病药物的新平台。
