Interference with the mitochondrial bioenergetics fuels reprogramming to pluripotency via facilitation of the glycolytic transition.
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.
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.
Myung Jin
MJ
Son
Bo Ram
BR
Jeong
Youjeong
Y
Kwon
Yee Sook
YS
Cho
D000818:Animals; D065150:Cellular Reprogramming; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006019:Glycolysis; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*
Bioenergetics; Glycolysis; Mitochondria; Reprogramming; iPSCs