Glycolysis: a bioenergetic or a survival pathway?

Trends Biochem Sci. 2010 Mar;35(3):145-9. doi: 10.1016/j.tibs.2009.10.006. Epub 2009 Dec 16.


Following inhibition of mitochondrial respiration neurons die rapidly, whereas astrocytes utilize glycolytically-generated ATP to increase their mitochondrial membrane potential, thus becoming more resistant to pro-apoptotic stimuli. Neurons are unable to increase glycolysis due to the lack of activity of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, isoform 3 (PFKFB3). In neurons, PFKFB3 is degraded constantly via the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)- CDH1. Glucose metabolism in neurons is directed mainly to the pentose phosphate pathway, leading to regeneration of reduced glutathione. In addition to their relevance to brain physiology and pathophysiology, these observations suggest that APC/C-CDH1 might link activation of glycolysis and cell proliferation as it is also involved in the regulation of cell cycle proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Brain / cytology
  • Brain / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Energy Metabolism*
  • Glucose / metabolism
  • Glycolysis / physiology*
  • Neurons / metabolism*
  • Phosphofructokinase-2 / genetics
  • Phosphofructokinase-2 / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism


  • Cell Cycle Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Phosphofructokinase-2
  • Glucose