Right place, right time: localisation and assembly of the NLRP3 inflammasome

The NLRP3 inflammasome is a multimeric protein complex that cleaves caspase-1 and the pro-inflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. Dysregulated NLRP3 inflammasome signalling is linked to several chronic inflammatory and autoimmune conditions; thus, understanding the activation mechanisms of the NLRP3 inflammasome is essential. Studies over the past few years have implicated vital roles for distinct intracellular organelles in both the localisation and assembly of the NLRP3 inflammasome. However, conflicting reports exist. Prior to its activation, NLRP3 has been shown to be resident in the endoplasmic reticulum (ER) and cytosol, although, upon activation, the NLRP3 inflammasome has been shown to assemble in the cytosol, mitochondria, and mitochondria-associated ER membranes by different reports. Finally, very recent work has suggested that NLRP3 may be localised on or adjacent to the Golgi apparatus and that release of mediators from this organelle may contribute to inflammasome assembly. Therefore, NLRP3 may be strategically placed on or in close proximity to these subcellular compartments to both sense danger signals originating from these organelles and use the compartment as a scaffold to assemble the complex. Understanding where and when NLRP3 inflammasome assembly occurs may help identify potential targets for treatment of NLRP3-related disorders.