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Nat Commun. 2016 Mar 31;7:11124. doi: 10.1038/ncomms11124.

Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.

Author information

1
Departamento de Biología Celular, Universidad de Valencia, Burjassot 46100, Spain.
2
Departamento de Bioquímica y Biología Molecular, Universidad de Valencia, Burjassot 46100, Spain.
3
Unidad de Hepatología Experimental, CIBERehd, Instituto de Investigación Sanitaria La Fe, Valencia 46026, Spain.
4
Centre de Medicina Regenerativa de Barcelona, Barcelona 08003, Spain.
5
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid 28029, Spain.
6
Institució Catalana de Recerca i Estudis Avançats, Barcelona 08010, Spain.

Abstract

During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. Drp1 phosphorylation depends on Erk activation in early reprogramming, which occurs, at least in part, due to downregulation of the MAP kinase phosphatase Dusp6. Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency.

PMID:
27030341
PMCID:
PMC4821885
DOI:
10.1038/ncomms11124
[Indexed for MEDLINE]
Free PMC Article

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