title: Dysfunctional mitochondrial fission impairs cell reprogramming.
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.
authors.affiliation: a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Prieto
authors.affiliation: a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: León
authors.affiliation: a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Ponsoda
authors.affiliation: b Computational Genomics Department , Centro de Investigación Principe Felipe , Valencia , Spain.|c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.affiliation: d Unidad de Hepatología Experimental, CIBEREHD, IIS La Fe. , Valencia , Spain.
authors.forename: Roque
authors.initials: R
authors.lastname: Bort
authors.affiliation: e Unidad Central de Investigación-INCLIVA, Universidad de Valencia , Valencia , Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Serna
authors.affiliation: c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain.|f Institut de Recerca Pediàtrica Hospital San Joan de Déu , Barcelona , Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Barneo-Muñoz
authors.affiliation: c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain.|f Institut de Recerca Pediàtrica Hospital San Joan de Déu , Barcelona , Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Palau
authors.affiliation: b Computational Genomics Department , Centro de Investigación Principe Felipe , Valencia , Spain.|c CIBER de Enfermedades Raras (CIBERER), ISCIII , Valencia , Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-García
authors.affiliation: a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.
authors.forename: Josema
authors.initials: J
authors.lastname: Torres
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D065150:Cellular Reprogramming / Q000187:drug effects; D004249:DNA Damage; D016195:G2 Phase / Q000187:drug effects; D055785:Gene Knockdown Techniques; D051379:Mice; D063154:Mitochondrial Dynamics / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors
keywords: Gdap1; cell reprogramming; iPS cells; mitochondrial fission; pluripotency