Sweet nothings: sensing of sugar metabolites controls T cell function

Abstract

Signal transduction and metabolism cooperate to control cell fate, but mechanisms that link metabolic substrates to functional decisions are elusive. Now, Chang et al. (2013) in Cell provide a mechanism whereby available sugars dictate metabolic pathways in activated T cells and direct a nonmetabolic regulatory function of glyceraldehyde-3-phosphate dehydrogenase.

Figure 1. Glyceraldehyde 3-Phosphate determines GAPDH suppression of IFN-γ translation

Glucose and galactose were found to differentially enter the glycolytic pathway and regulate GAPDH. Galactose requires additional ATP to enter metabolic pathways and did not appear to undergo glycolysis but rather enther the Pentose Phosphate Pathway (PPP). When G3P was limiting with galactose, GAPDH associated with the 3′UTR of IFNγ mRNA and prevented translation. Increased glycolytic flux and G3P provided by glucose availability, however, relieved GAPDH inhibition of IFNγ mRNA translation. Thus aerobic glycolysis provides a nutrient signal through G3P to directly modify cytokine production.