Ambient ozone exposure induces ROS related-mitophagy and pyroptosis via NLRP3 inflammasome activation in rat lung cells

• Published in: Ecotoxicology and environmental safety Vol. 240; p. 113663
• Main Authors: Tian, Lei, Li, Ning, Li, Kang, Tan, Yizhe, Han, Jie, Lin, Bencheng, Lai, Wenqing, Liu, Huanliang, Shi, Yue, Xi, Zhuge, Liu, Xiaohua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.07.2022; Elsevier
• Subjects: Lung toxicity; Mitophagy; Ozone; Pyroptosis; Reactive oxygen species; Lung toxicity; Ozone; Reactive oxygen species; Pyroptosis; Mitophagy
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.113663

To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome. •Ozone exposure can lead to pulmonary mitochondrial dysfunction in vivo and in vitro.•Ozone exposure can lead to mitophagy in lung, and ROS is involved in this process.•ROS induce mitophagy through the activation of the PINK1/Parkin signaling pathway.•Mitophagy induced by ozone can induce pyroptosis through the activation of NLRP3 inflammasome in lung.