Mitochondrial reactive oxygen species-NOD-like receptor protein 3 axis (mROS-NLRP3 axis)

The mROS-NLRP3 axis is a pivotal signaling pathway linking mitochondrial stress to the innate immune response. It is characterized by the production of mitochondrial reactive oxygen species (mROS), which act as a key secondary signal for the activation of the NLRP3 inflammasome complex. This complex consists of the sensor protein NLRP3, the adapter protein ASC, and the protease caspase-1. Upon activation, the axis facilitates the cleavage of pro-inflammatory cytokines IL-1β and IL-18 into their mature, bioactive forms and can trigger gasdermin D-mediated pyroptosis. Dysregulation of this axis is implicated in a wide range of inflammatory and metabolic disorders, including atherosclerosis, gout, and Alzheimer's disease. Therapeutic strategies targeting this pathway include mitochondrial-targeted antioxidants to reduce mROS levels and small-molecule inhibitors of NLRP3. These interventions aim to dampen chronic inflammation while ideally preserving necessary immune surveillance functions.

Other names

mROS-NLRP3 signaling pathwayMitochondrial ROS-NLRP3 pathwaymtROS-NLRP3 axismROS-mediated NLRP3 activationmROS-TXNIP-NLRP3 axis

Inhibition of mitochondrial ROS production, scavenging of mitochondrial ROS to prevent inflammasome triggering, or direct inhibition of NLRP3 ATPase activity to prevent complex assembly