Dysfunctional mitochondrial fission impairs cell reprogramming.

TitleDysfunctional mitochondrial fission impairs cell reprogramming.
Publication TypeJournal Article
Year of Publication2016
AuthorsPrieto, J, León, M, Ponsoda, X, Garcia-Garcia, F, Bort, R, Serna, E, Barneo-Muñoz, M, Palau, F, Dopazo, J, López-García, C, Torres, J
JournalCell Cycle
Date Published2016 Dec
KeywordsAnimals; Cell Cycle Checkpoints; Cellular Reprogramming; DNA Damage; G2 Phase; Gene Knockdown Techniques; Mice; Mitochondrial Dynamics; Mitosis; Nerve Tissue Proteins; Pluripotent Stem Cells; Transcription Factors

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.

Alternate JournalCell Cycle
PubMed ID27753531
PubMed Central IDPMC5176137