Microplastic-Induced DRP1-BAX Interaction Contributes to Mitochondrial Apoptosis in Lung Epithelial Cells

As pervasive environmental pollutants, microplastics-(MPs) have been identified in marine ecosystems, food, air, and drinking water, prompting serious consideration of their probable adverse effects on public health. Emerging evidence associates MPs with respiratory risks, yet their toxic mechanisms in lung tissue remain poorly elucidated. In this investigation, C57BL/6n mice were exposed to 10 mg/kg polystyrene microplastics (PS-MPs) with varying sizes (0.2 μm, 1 μm) individually or combined every 2 days for 14 days. The results exhibited that PS-MPs exposure induced the size-dependent respiratory dysfunction in mice, characterized by oxidative stress and pulmonary epithelial apoptosis. In vitro experiments revealed that PS0.2 internalization of MLE-12 cells triggered apoptosis via increasing BAX-mediated cytochrome C release and caspase-3 activation. Mechanistically, PS0.2 promoted DRP1-dependent mitochondrial fission, leading to membrane potential collapse and respiratory chain impairment. The administration of Mdivi-1/si-DRP1 inhibition of DRP1 effectively attenuated mitochondrial fragmentation and apoptosis. Additionally, molecular docking analysis and coimmunoprecipitation revealed that DRP1 directly interacts with BAX to facilitate oligomerization of this pro-apoptotic protein, promoting the release of cytochrome C. These findings establish a novel DRP1-BAX signaling axis in MPs-induced pulmonary toxicity and the first molecular link between PS-MP size and mitochondrial apoptosis via DRP1-BAX oligomerization into environmental particle-related respiratory pathogenesis.