Dysfunctional mitochondrial fission impairs cell reprogramming
Por:
Prieto J, León M, Ponsoda X, García-García F, Bort R, Serna E, Barneo-Muñoz M, Palau F, Dopazo J, López-García C and Torres J
Publicada:
1 ene 2016
Ahead of Print:
18 oct 2016
Resumen:
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.
Filiaciones:
Prieto J:
a Department of Biología Celular, Biología Funcional y Antropología Física , Universitat de València , Burjassot , Spain
León M:
a Department of Biología Celular, Biología Funcional y Antropología Física , Universitat de València , Burjassot , Spain
Ponsoda X:
a Department of Biología Celular, Biología Funcional y Antropología Física , Universitat de València , Burjassot , Spain
García-García F:
b Computational Genomics Department , Centro de Investigación Principe Felipe , Valencia , Spain
c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain
Bort R:
d Unidad de Hepatología Experimental, CIBEREHD, IIS La Fe. , Valencia , Spain
Serna E:
e Unidad Central de Investigación-INCLIVA, Universidad de Valencia , Valencia , Spain
Barneo-Muñoz M:
c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain
f Institut de Recerca Pediàtrica Hospital San Joan de Déu , Barcelona , Spain
Palau F:
c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain
f Institut de Recerca Pediàtrica Hospital San Joan de Déu , Barcelona , Spain
Dopazo J:
b Computational Genomics Department , Centro de Investigación Principe Felipe , Valencia , Spain
c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain
López-García C:
a Department of Biología Celular, Biología Funcional y Antropología Física , Universitat de València , Burjassot , Spain
Torres J:
a Department of Biología Celular, Biología Funcional y Antropología Física , Universitat de València , Burjassot , Spain
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