Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science & Technology, 217 Gajungro, Yuseong-gu, Daejeon 305-333, Republic of Korea.
Int J Biochem Cell Biol. 2013 Nov;45(11):2512-8. doi: 10.1016/j.biocel.2013.07.023. Epub 2013 Aug 9.
The switch in cell metabolism from oxidative phosphorylation to glycolysis is critical for the reprogramming of cells to pluripotency. Here, we demonstrate that the disturbance of mitochondrial metabolism by canonical mitochondrial inhibitors enhances metabolic reprogramming toward a glycolytic state, enabling the highly efficient generation of induced pluripotent stem cells. This interference with mitochondrial bioenergetics resulted in enriched reprogrammable subpopulations and accelerated the conversion of refractory intermediates to pluripotent states without requiring additional genetic or epigenetic modifications. Conversely, the reprogramming efficiency and accelerated reprogramming kinetics promoted by mitochondrial inhibition were obstructed by glycolysis inhibitors. We suggest that changes in mitochondrial bioenergetics are a novel mechanism involved in the regulation of cell fate and, more importantly, in the reprogramming of cells to pluripotency.
细胞代谢从氧化磷酸化向糖酵解的转变对于细胞重编程为多能性至关重要。在这里，我们证明了经典线粒体抑制剂对线粒体代谢的干扰增强了向糖酵解状态的代谢重编程，从而能够高效地产生诱导多能干细胞。这种对线粒体生物能量学的干扰导致了可重编程亚群的富集，并加速了难治性中间产物向多能状态的转化，而不需要额外的遗传或表观遗传修饰。相反，糖酵解抑制剂会阻碍线粒体抑制所促进的重编程效率和加速重编程动力学。我们认为，线粒体生物能量学的变化是参与细胞命运调控的一种新机制，更重要的是，是参与细胞重编程为多能性的一种新机制。
