TY - JOUR T1 - Dysfunctional mitochondrial fission impairs cell reprogramming. JF - Cell Cycle Y1 - 2016 A1 - Prieto, Javier A1 - León, Marian A1 - Ponsoda, Xavier A1 - Garcia-Garcia, Francisco A1 - Bort, Roque A1 - Serna, Eva A1 - Barneo-Muñoz, Manuela A1 - Palau, Francesc A1 - Dopazo, Joaquin A1 - López-García, Carlos A1 - Torres, Josema KW - Animals KW - Cell Cycle Checkpoints KW - Cellular Reprogramming KW - DNA Damage KW - G2 Phase KW - Gene Knockdown Techniques KW - Mice KW - Mitochondrial Dynamics KW - Mitosis KW - Nerve Tissue Proteins KW - Pluripotent Stem Cells KW - Transcription Factors AB -

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.

VL - 15 IS - 23 U1 - https://www.ncbi.nlm.nih.gov/pubmed/27753531?dopt=Abstract ER -