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

EMBO Rep. 2013 Jul;14(7):638-44. doi: 10.1038/embor.2013.72. Epub 2013 May 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPase Inhibitory Protein
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Colon / cytology
  • Colon / metabolism
  • Energy Metabolism*
  • Gene Expression Regulation
  • Gene Silencing
  • Glycolysis
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Osteocytes / cytology
  • Osteocytes / metabolism*
  • Osteogenesis / genetics
  • Oxidative Phosphorylation
  • Prostate / cytology
  • Prostate / metabolism
  • Proteins / antagonists & inhibitors
  • Proteins / genetics*
  • Proteins / metabolism
  • Proteolysis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*

Substances

  • Biomarkers
  • Proteins
  • RNA, Small Interfering