Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming

Clifford D.L. Folmes, Timothy J. Nelson, Almudena Martinez-Fernandez, D. Kent Arrell, Jelena Zlatkovic Lindor, Petras P. Dzeja, Yasuhiro Ikeda, Carmen Perez-Terzic, Andre Terzic

Research output: Contribution to journalArticlepeer-review

569 Scopus citations

Abstract

The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, stemness factor-mediated nuclear reprogramming reverted mitochondrial networks into cristae-poor structures. Metabolomic footprinting and fingerprinting distinguished derived pluripotent progeny from parental fibroblasts according to elevated glucose utilization and production of glycolytic end products. Temporal sampling demonstrated glycolytic gene potentiation prior to induction of pluripotent markers. Functional metamorphosis of somatic oxidative phosphorylation into acquired pluripotent glycolytic metabolism conformed to an embryonic-like archetype. Stimulation of glycolysis promoted, while blockade of glycolytic enzyme activity blunted, reprogramming efficiency. Metaboproteomics resolved upregulated glycolytic enzymes and downregulated electron transport chain complex I subunits underlying cell fate determination. Thus, the energetic infrastructure of somatic cells transitions into a required glycolytic metabotype to fuel induction of pluripotency.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalCell Metabolism
Volume14
Issue number2
DOIs
StatePublished - Aug 3 2011

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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