When Hexokinase Gets that NAG-ing Feeling…

Abstract

Immune cell recognition of bacterial products usually occurs via specific pattern recognition receptors, but new research recently published in Cell by Wolf et al. (2016) demonstrates that the glycolytic enzyme hexokinase can act as an innate immune sensor by binding to bacterial derived N-acetylglucosamine (NAG).

Figure 1. N-acetylglucosamine Causes NLRP3 Inflammasome Activation by Binding to Hexokinase

Hexokinase is a glycolytic enzyme that converts glucose to glucose-6-phosphate (G6P). New research from Wolf et al. (2016) demonstrates that bacterial N-acetylglucosamine (NAG), derived from phagocytosed Gram-positive bacteria, can bind to and inhibit hexokinase (HK) in macrophages. NAG binding can also cause the dissociation of HK from voltage-dependent anion channels (VDACs) on the outer mitochondrial membrane. This in turn leads to NLRP3 inflammasome activation and IL-1β release by an undetermined mechanism, which could be related to release of reactive oxygen species (ROS), mitochondrial DNA (mtDNA), cardiolipin, or some other factor (???).