IL-1β and IL-18 are pro-inflammatory cytokines that play a critical role in the response to a diverse array of injuries and infections. Accordingly, the production of these potent cytokines is tightly regulated at transcriptional and post-translational levels through control of both maturation and secretion. The maturation of these cytokines is regulated by caspase-1 inflammasomes. Several members of the Nod-like receptor (NLR) family of intracellular sensors, including NLRP3, NLRC4 and NLRP1, play critical roles in inflammasome regulation. However, the nature of the physiological cues that trigger inflammasome activation remain incompletely understood.

A recent study by Zhou et al. examined this important question in the context of activation of the NLRP3 inflammasome [1]. Zhou et al. demonstrated that generation of mitochondrial reactive oxygen species (ROS) led to NLRP3 inflammasome activation, and treatment of macrophages with NLRP3 activators resulted in the recruitment of NLRP3 to mitochondria-associated ER membranes (MAMs) where the protein recruited the ASC adaptor critical for inflammasome formation (Figure 1). Furthermore, autophagy limited NLRP3 inflammasome activation by targeting ROS-producing mitochondria (Figure 1). Therefore, this study provides a fun-