Greasing the wheels of inflammasome formation: regulation of NLRP3 function by S-linked fatty acids

NLRP3 is an inflammasome seeding pattern recognition receptor that initiates a pro-inflammatory signalling cascade in response to changes in intracellular homeostasis that are indicative of bacterial infection or tissue damage. Several types of post-translational modification (PTM) have been identified that are added to NLRP3 to regulate its activity. Recent progress has revealed that NLRP3 is subject to a further type of PTM, S-acylation (or palmitoylation), which involves the reversible addition of long-chain fatty acids to target cysteine residues by opposing sets of enzymes. This review provides an overview of recent studies that have identified S-acylation as an important modifier of NLRP3 function. The essential role of S-acylation in the recruitment of NLRP3 to intracellular membranes and the consequences of S-acylation-dependent membrane recruitment on NLRP3 localisation and activation are discussed in detail.