6533b830fe1ef96bd12972c1
RESEARCH PRODUCT
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.
Marian LeónXavier PonsodaJavier PrietoRaquel Ferrer-lorenteAngel RayaCarlos Lopez-garciaRamon SendraJosema TorresRoque Bortsubject
0301 basic medicineDynaminsSomatic cellMAP Kinase Signaling SystemScienceCèl·lulesCellInduced Pluripotent Stem CellsKruppel-Like Transcription FactorsGeneral Physics and AstronomyBiologyMitochondrionMitochondrial DynamicsGeneral Biochemistry Genetics and Molecular BiologyMitocondrisArticleCell LineProto-Oncogene Proteins c-myc03 medical and health sciencesKruppel-Like Factor 4MiceMitophagymedicineAnimalsPhosphorylationInduced pluripotent stem cellGeneticsMultidisciplinarySOXB1 Transcription FactorsQGeneral ChemistryCellular ReprogrammingCell biologyMitochondria030104 developmental biologymedicine.anatomical_structurePhosphorylationMitochondrial fissionReprogrammingOctamer Transcription Factor-3description
During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. Drp1 phosphorylation depends on Erk activation in early reprogramming, which occurs, at least in part, due to downregulation of the MAP kinase phosphatase Dusp6. Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 | Nature communications |