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

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...

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Autores principales: Prieto, Javier, León, Marian, Ponsoda, Xavier, Sendra, Ramón, Bort, Roque, Ferrer-Lorente, Raquel, Raya, Angel, López-García, Carlos, Torres, Josema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821885/
https://www.ncbi.nlm.nih.gov/pubmed/27030341
http://dx.doi.org/10.1038/ncomms11124
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author Prieto, Javier
León, Marian
Ponsoda, Xavier
Sendra, Ramón
Bort, Roque
Ferrer-Lorente, Raquel
Raya, Angel
López-García, Carlos
Torres, Josema
author_facet Prieto, Javier
León, Marian
Ponsoda, Xavier
Sendra, Ramón
Bort, Roque
Ferrer-Lorente, Raquel
Raya, Angel
López-García, Carlos
Torres, Josema
author_sort Prieto, Javier
collection PubMed
description 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.
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spelling pubmed-48218852016-04-17 Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming Prieto, Javier León, Marian Ponsoda, Xavier Sendra, Ramón Bort, Roque Ferrer-Lorente, Raquel Raya, Angel López-García, Carlos Torres, Josema Nat Commun Article 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. Nature Publishing Group 2016-03-31 /pmc/articles/PMC4821885/ /pubmed/27030341 http://dx.doi.org/10.1038/ncomms11124 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Prieto, Javier
León, Marian
Ponsoda, Xavier
Sendra, Ramón
Bort, Roque
Ferrer-Lorente, Raquel
Raya, Angel
López-García, Carlos
Torres, Josema
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title_full Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title_fullStr Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title_full_unstemmed Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title_short Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming
title_sort early erk1/2 activation promotes drp1-dependent mitochondrial fission necessary for cell reprogramming
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821885/
https://www.ncbi.nlm.nih.gov/pubmed/27030341
http://dx.doi.org/10.1038/ncomms11124
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