Dysfunctional mitochondrial fission impairs cell reprogramming |
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| Authors: | Javier Prieto Marian León Xavier Ponsoda Francisco García-García Roque Bort Eva Serna |
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| Institution: | 1. Department of Biología Celular, Biología Funcional y Antropología Física, Universitat de València, Burjassot, Spain;2. Computational Genomics Department, Centro de Investigación Principe Felipe, Valencia, Spain;3. CIBER de Enfermedades Raras (CIBERER), ISCIII, Valencia, Spain;4. Unidad de Hepatología Experimental, CIBEREHD, IIS La Fe., Valencia, Spain;5. Unidad Central de Investigación-INCLIVA, Universidad de Valencia, Valencia, Spain |
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| 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. |
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| Keywords: | cell reprogramming Gdap1 iPS cells mitochondrial fission pluripotency |
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