• Ozone exposure triggers NLRP3 inflammasome activation in alveolar macrophages, leading to mitochondrial dysfunction and acute lung inflammatory injury.
• Mitochondrial homeostasis disruption in alveolar macrophages is characterized by increased mitochondrial number, mtROS, and DRP1, alongside decreased OPA1, NRF1, and mtDNA.
• Genetic ablation of NLRP3 or Caspase-1 alleviates ozone-induced lung inflammation and mitochondrial imbalance, confirming the inflammasome's central role.
• Targeting NLRP3 inflammasome-mediated mitochondrial disruption in alveolar macrophages offers a novel therapeutic strategy for ozone-induced lung injury.