%0 Journal Article %J Cell Cycle %D 2016 %T Dysfunctional mitochondrial fission impairs cell reprogramming. %A Prieto, Javier %A León, Marian %A Ponsoda, Xavier %A Garcia-Garcia, Francisco %A Bort, Roque %A Serna, Eva %A Barneo-Muñoz, Manuela %A Palau, Francesc %A Dopazo, Joaquin %A López-García, Carlos %A Torres, Josema %K Animals %K Cell Cycle Checkpoints %K Cellular Reprogramming %K DNA Damage %K G2 Phase %K Gene Knockdown Techniques %K Mice %K Mitochondrial Dynamics %K Mitosis %K Nerve Tissue Proteins %K Pluripotent Stem Cells %K Transcription Factors %X

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.

%B Cell Cycle %V 15 %P 3240-3250 %8 2016 Dec %G eng %N 23 %1 https://www.ncbi.nlm.nih.gov/pubmed/27753531?dopt=Abstract %R 10.1080/15384101.2016.1241930