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Dysfunctional mitochondrial fission impairs cell reprogramming

Javier Prieto1, Marian León1, Xavier Ponsoda1

  • 1a Department of Biología Celular , Biología Funcional y Antropología Física, Universitat de València , Burjassot , Spain.

Cell Cycle (Georgetown, Tex.)
|October 19, 2016
PubMed

Insights

Mitochondrial fission, regulated by factors like MiD51 and Gdap1, is crucial for cell reprogramming. Its absence causes cell cycle arrest, hindering reprogramming independently of DNA damage.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Stem Cell Reprogramming

Background:

  • Mitochondrial fission is essential for cellular processes, including early reprogramming.
  • The specific factors controlling Drp1 recruitment to mitochondria during reprogramming were previously unknown.

Purpose of the Study:

  • To identify key regulators of Drp1-mediated mitochondrial fission during cell reprogramming.
  • To investigate the role of Gdap1 in mitochondrial fission and its impact on cell reprogramming.

Main Methods:

  • RNA interference (RNAi) screening to identify factors regulating mitochondrial dynamics.
  • Analysis of cells from Gdap1-null mice.
  • Microarray analysis and cell cycle profiling.
  • High-Content imaging for DNA damage assessment.

Main Results:

  • MiD51, Gdap1, and Mff were identified as key regulators of Drp1 recruitment to mitochondria.
  • Gdap1-null cells exhibited significant downregulation of cell cycle pathways during reprogramming.
  • Gdap1-null cells displayed a G2/M growth arrest.
  • The observed growth arrest was independent of DNA damage.

Conclusions:

  • Gdap1 plays a critical role in regulating mitochondrial fission during cell reprogramming.
  • Impaired mitochondrial fission due to lack of Gdap1 disrupts cell cycle progression.
  • This disruption leads to a DNA damage-independent G2/M arrest, hindering efficient cell reprogramming.
Keywords:
Gdap1cell reprogrammingiPS cellsmitochondrial fissionpluripotency

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