MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism

Stem Cell Reports. 2016 Jul 12;7(1):1-10. doi: 10.1016/j.stemcr.2016.05.012. Epub 2016 Jun 23.

Abstract

Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Cellular Reprogramming / genetics
  • Electron Transport Complex II / genetics*
  • Electron Transport Complex II / metabolism
  • Energy Metabolism / genetics
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • MicroRNAs / genetics*
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Signal Transduction

Substances

  • MIRN31 microRNA, human
  • MicroRNAs
  • Electron Transport Complex II
  • SDHA protein, human