Dysfunctional mitochondrial fission impairs cell reprogramming
Por:
J. PRIETO, M. LEON, X. PONSODA, F. GARCÍA, R. BORT, E. SERNA, M. BARNEO-MUNOZ, F. PALAU, J. DOPAZO, C. LOPEZ-GARCIA and J. TORRES
Publicada:
1 ene 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:
J. PRIETO:
Univ Valencia, Dept Biol Celular Biol Func & Antropol Fis, Burjassot, Spain
:
Univ Valencia, Dept Biol Celular Biol Func & Antropol Fis, Burjassot, Spain
X. PONSODA:
Univ Valencia, Dept Biol Celular Biol Func & Antropol Fis, Burjassot, Spain
:
Ctr Invest Principe Felipe, Computat Genom Dept, Valencia, Spain
ISCIII, CIBER Enfermedades Raras CIBERER, Valencia, Spain
R. BORT:
IIS La Fe, CIBEREHD, Unidad Hepatol Expt, Valencia, Spain
E. SERNA:
Univ Valencia, Unidad Cent Invest INCLIVA, Valencia, Spain
M. BARNEO-MUNOZ:
ISCIII, CIBER Enfermedades Raras CIBERER, Valencia, Spain
Hosp San Joan de Deu, Inst Recerca Pediat, Barcelona, Spain
:
ISCIII, CIBER Enfermedades Raras CIBERER, Valencia, Spain
Hosp San Joan de Deu, Inst Recerca Pediat, Barcelona, Spain
:
Ctr Invest Principe Felipe, Computat Genom Dept, Valencia, Spain
ISCIII, CIBER Enfermedades Raras CIBERER, Valencia, Spain
C. LOPEZ-GARCIA:
Univ Valencia, Dept Biol Celular Biol Func & Antropol Fis, Burjassot, Spain
J. TORRES:
Univ Valencia, Dept Biol Celular Biol Func & Antropol Fis, Burjassot, Spain
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