02242nas a2200409 4500008004100000022001400041245006800055210006700123260001300190300001400203490000700217520102100224653001201245653002701257653002701284653001501311653001301326653003001339653000901369653002701378653001201405653002601417653002701443653002601470100001901496700001801515700002001533700002901553700001601582700001501598700002701613700002001640700002001660700002701680700001901707856010601726 2016 eng d a1551-400500aDysfunctional mitochondrial fission impairs cell reprogramming.0 aDysfunctional mitochondrial fission impairs cell reprogramming c2016 Dec a3240-32500 v153 a
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.
10aAnimals10aCell Cycle Checkpoints10aCellular Reprogramming10aDNA Damage10aG2 Phase10aGene Knockdown Techniques10aMice10aMitochondrial Dynamics10aMitosis10aNerve Tissue Proteins10aPluripotent Stem Cells10aTranscription Factors1 aPrieto, Javier1 aLeón, Marian1 aPonsoda, Xavier1 aGarcia-Garcia, Francisco1 aBort, Roque1 aSerna, Eva1 aBarneo-Muñoz, Manuela1 aPalau, Francesc1 aDopazo, Joaquin1 aLópez-García, Carlos1 aTorres, Josema uhttps://www.clinbioinfosspa.es/content/dysfunctional-mitochondrial-fission-impairs-cell-reprogramming