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Degradation of IF1 controls energy metabolism during osteogenic differentiation of stem cells

María Sánchez‐Aragó, Javier García‐Bermúdez, Inmaculada Martínez‐Reyes, Fulvio Santacatterina, José M Cuezva

Author Affiliations

  1. María Sánchez‐Aragó1,
  2. Javier García‐Bermúdez1,
  3. Inmaculada Martínez‐Reyes1,
  4. Fulvio Santacatterina1 and
  5. José M Cuezva*,1
  1. 1 Departamento de Biología Molecular, Centro de Biología Molecular Servero Ochoa, CSIC‐UAM, Centro de Biología Molecular Severo Ochoa, CSIC‐UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Centro de Investigación Hospital 12 de Octubre, ISCIII, Universidad Autónoma de Madrid, 28049, Madrid, Spain
  1. *Corresponding author. Tel:+34 91 1964618; Fax:+34 91 1964420; E-mail: jmcuezva{at}
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Differentiation of human mesenchymal stem cells (hMSCs) requires the rewiring of energy metabolism. Herein, we demonstrate that the ATPase inhibitory factor 1 (IF1) is expressed in hMSCs and in prostate and colon stem cells but is not expressed in the differentiated cells. IF1 inhibits oxidative phosphorylation and regulates the activity of aerobic glycolysis in hMSCs. Silencing of IF1 in hMSCs mimics the metabolic changes observed in osteocytes and accelerates cellular differentiation. Activation of IF1 degradation acts as the switch that regulates energy metabolism during differentiation. We conclude that IF1 is a stemness marker important for maintaining the quiescence state.

  • Received December 26, 2012.
  • Revision received April 24, 2013.
  • Accepted May 10, 2013.
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