Glycolysis and NLRP3 inflammasome activation in diseases

To adapt to environmental changes or external stimuli, cells often undergo a shift in the way they metabolize energy, a process known as metabolic reprogramming. Glycolytic reprogramming has emerged as a central regulatory node among the overall adaptive rewiring of energy metabolism and represents a fundamental biological strategy for maintaining functional plasticity and determining cell fate. The NLRP3 inflammasome is a multiprotein complex that drives pyroptosis-a programmed cell death mode characterized by cell swelling, plasma membrane perforation, and proinflammatory cytokine release (Zhong et al. in Int J Biol Sci. 19:242-257, 2023; Lin et al. in Front Immunol 11:580593, 2020; Hoque et al. in Gastroenterology 146:1763-1774, 2014; Lee et al. in Cell Death Differ 31:1679-1694, 2024; You et al. in Ecotoxicol Environ Saf 283:116952, 2024). However, evidence reveals that glycolytic reprogramming and NLRP3 inflammasome activation engage in reciprocal regulation across diverse cell types and disease states. This review synthesizes recent advances elucidating how glycolytic enzymes (e.g., HKs and PKM2) and metabolic intermediates (e.g., lactate) orchestrate NLRP3 activation. By bridging metabolic control with inflammatory signaling, these findings establish the glycolysis-NLRP3 axis as a promising therapeutic target for modulating cellular fate decisions in inflammatory pathologies.