Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation

How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon…

• CI
  California Institute for Regenerative Medicine

  Award: TR2-01778
• GH
  G. Harold and Leila Y. Mathers Charitable Foundation
• LM
  Leona M. and Harry B. Helmsley Charitable Trust

  Award: #2012-PG-MED002
• JF
  JPB Foundation
• NI
  National Institutes of Health

  Awards: CA80100, CA14195, CA82683