Cardiolipin Provides a Platform for Caspase-1 Activation and NLRP3 Inflammasome Assembly

The NLRP3 inflammasome promotes innate immunity through Caspase-1 activation and IL-1β and IL-18 maturation. Two-step NLRP3 activation requires an initial NFκB-activating priming stimulus and secondary agonist which induces cation flux and mitochondrial stress. However, the dynamics of inflammasome assembly and extent of mitochondrial disruption required for NLRP3 activation remain uncertain. NLRP3 interacts with mitochondrial cardiolipin, and we hypothesized cardiolipin could activate NLRP3 in vitro.