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Title 

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency

Authors 

Myung Jin SonYoujeong KwonMi Young SonBinna SeolHoon Sung ChoiS W RyuC ChoiYee Sook Cho

Publisher 

Nature Publishing Group

Issue Date 

2015

Citation 

Cell Death and Differentiation, vol. 22, no. 12, pp. 1957-1969

Abstract 

Cell reprogramming technology has allowed the in vitro control of cell fate transition, thus allowing for the generation of highly desired cell types to recapitulate in vivo developmental processes and architectures. However, the precise molecular mechanisms underlying the reprogramming process remain to be defined. Here, we show that depleting p53 and p21, which are barriers to reprogramming, yields a high reprogramming efficiency. Deletion of these factors results in a distinct mitochondrial background with low expression of oxidative phosphorylation subunits and mitochondrial fusion proteins, including mitofusin 1 and 2 (Mfn1/2). Importantly, Mfn1/2 depletion reciprocally inhibits the p53-p21 pathway and promotes both the conversion of somatic cells to a pluripotent state and the maintenance of pluripotency. Mfn1/2 depletion facilitates the glycolytic metabolic transition through the activation of the Ras-Raf and hypoxia-inducible factor 1 (HIF1) signaling at an early stage of reprogramming. HIF1 is required for increased glycolysis and reprogramming by Mfn1/2 depletion. Taken together, these results demonstrate that Mfn1/2 constitutes a new barrier to reprogramming, and that Mfn1/2 ablation facilitates the induction of pluripotency through the restructuring of mitochondrial dynamics and bioenergetics.

ISSN 

1350-9047

Link 

http://dx.doi.org/10.1038/cdd.2015.43

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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