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Neuronal metabolism

A question of balance

Nature Reviews Neuroscience volume 10, pages 472–473 (2009)Cite this article

Neurons contain lower levels of a key glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), than other cells, and it is assumed that this underlies the reduced activity of the glycolytic pathway in these cells. Here, the authors found that neurons express normal amounts of Pfkfb3 mRNA, suggesting that they downregulate the levels of the enzyme post-transcriptionally.

The authors demonstrated that inhibiting proteasome activity increased the levels of ubiquitylated PFKFB3 in cultured rat neurons, suggesting that the ubiquitin–proteasome system normally degrades the enzyme. The presence of specific motifs in the PFKFB3 amino acid sequence suggested that the E3 ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), in conjunction with the adaptor protein CDH1, targets the protein for ubiquitylation. Indeed, when the authors knocked down CDH1 using small interfering RNA they increased both PFKFB3 levels and glycolysis in neurons. CDH1 levels were lower in astrocytes than in neurons, which may explain the relatively higher levels of PFKFB3 and glycolysis in astrocytes.

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ORIGINAL RESEARCH PAPER

  1. Herrero-Mendez, A. et al. The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C–Cdh1. Nature Cell Biol. 17 May 2009 (doi: 10.1038/ncb1881)

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  1. Katherine Whalley
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Whalley, K. A question of balance. Nat Rev Neurosci 10, 472–473 (2009). https://doi.org/10.1038/nrn2669

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