Dysfunctional mitochondrial fission impairs cell reprogramming.

Autors de IIS La Fe

• Javier Prieto Martinez

  Autor

• Montserrat León Fabregas

  Autor

• Xavier Ponsoda Marti

  Autor

• Francisco Garcia Garcia

  Autor

• Bernardo Roque Bort Martí

  Autor

• Eva Serna Garcia

  Autor

• Francesc Palau Martinez

  Autor

• Joaquin Dopazo Blazquez

  Autor

• Carlos Lopez Garcia

  Autor

Autors aliens a IIS La Fe

• Barneo-Muñoz M
• Torres J

Grups d'Investigació

• Hepatología experimental y Trasplante hepático

  Investigador Principal

  Laia Tolosa Pardo

• Neumología

  

  Leader

  Miguel Ángel Martínez García

Abstract

We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered a G2/M growth arrest in Gdap1-null cells undergoing reprogramming. High-Content analysis showed that this growth arrest was DNA damage-independent. We propose that lack of efficient mitochondrial fission impairs cell reprogramming by interfering with cell cycle progression in a DNA damage-independent manner.

Keywords

• Gdap1; cell reprogramming; iPS cells; mitochondrial fission; pluripotency