Metabolic regulatory nodes of the inflammasome and inflammatory cell death

Inflammation is a metabolically intensive and tightly regulated process, driven primarily by innate immune cells. Cellular metabolism actively instructs immune signaling and cell fate decisions. Bioenergetic pathways, including glycolysis, mitochondrial respiration, and the tricarboxylic acid cycle, reshape cytokine production and regulate inflammatory cell death pathways. In this review, we synthesize emerging evidence on how metabolic intermediates and pathways regulate inflammasome signaling and the execution of diverse inflammatory cell death modalities, including pyroptosis, necroptosis, PANoptosis, and ferroptosis. We propose that metabolic inputs-including redox balance, mitochondrial dynamics, and lipid modifications-constitute an interconnected metabolic regulatory network that determines the threshold and outcome of inflammatory signaling. This framework offers new insights into immunometabolic dysregulation and therapeutic strategies in inflammatory, infectious, and neoplastic diseases.