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Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury
Summary
Researchers found that inhaled polystyrene nanoplastics cause lung damage through a specific cell death process called ferroptosis, which involves iron buildup and oxidative stress in lung cells. The nanoplastics damaged mitochondria and triggered a chain reaction where the cell's iron storage was broken down, releasing harmful iron. Blocking this ferroptosis process with a drug called ferrostatin-1 reversed the lung damage in mice, pointing to a potential treatment approach.
Nanoplastics are a common type of contaminant in the air. However, no investigations have focused on the toxic mechanism of lung injury induced by nanoplastic exposure. In the present study, polystyrene nanoplastics (PS-NPs) caused ferroptosis in lung epithelial cells, which could be alleviated by ferrostatin-1, deferoxamine, and N-acetylcysteine. Further investigation found that PS-NPs disturbed mitochondrial structure and function and triggered autophagy. Mechanistically, oxidative stress-derived mitochondrial damage contributed to ferroptosis, and autophagy-dependent ferritinophagy was a pivotal intermediate link, resulting in ferritin degradation and iron ion release. Furthermore, inhibition of ferroptosis using ferrostatin-1 alleviated pulmonary and systemic toxicity to reverse the mouse lung injury induced by PS-NPs inhalation. Most importantly, the lung-on-a-chip was further used to clarify the role of ferroptosis in the PS-NPs-induced lung injury by visualizing the ferroptosis, oxidative stress, and alveolar-capillary barrier dysfunction at the organ level. In summary, our study indicated that ferroptosis was an important mechanism for nanoplastics-induced lung injury through different lung cells, mouse inhalation models, and three-dimensional-based lung-on-a-chip, providing an insightful reference for pulmonary toxicity assessment of nanoplastics.