Microplastics exacerbate ferroptosis via mitochondrial reactive oxygen species-mediated autophagy in chronic obstructive pulmonary disease.

ABSTRACT: Microplastics (MPs) induce mitochondrial dysfunction and iron accumulation, contributing to mitochondrial macroautophagy/autophagy and ferroptosis, which has increased susceptibility to the exacerbation of chronic obstructive pulmonary disease (COPD); however, the underlying mechanism remains unclear. We demonstrated that MPs intensified inflammation in COPD by enhancing autophagy-dependent ferroptosis (ADF) in vitro and in vivo. In the lung tissues of patients with COPD, the concentrations of MPs, especially polystyrene microplastics (PS-MPs), were significantly higher than that of the control group, as detected by pyrolysis gas chromatography mass spectrometry (Py-GCMS), with increased iron accumulation. The exposure to PS-MPs, 2 μm in size, resulted in their being deposited in the lungs of COPD model mice detected by optical in vivo imaging, and observed in bronchial epithelial cells traced by GFP-labeled PS-MPs. There were mitochondrial impairments accompanied by mitochondrial reactive oxygen species (mito-ROS) overproduction and significantly increased levels of lysosome biogenesis and acidification in pDHBE cells with PS-MP stimulation, triggering occurrence of ferritinophagy and enhancing ADF in COPD, which triggered acute exacerbation of COPD (AECOPD). Reestablishing autophagy-dependent ferroptosis via mitochondria-specific ROS scavenging or ferroptosis inhibition alleviated excessive inflammation and ameliorated AECOPD induced by PS-MPs. Collectively, our data initially revealed that MPs exacerbate ferroptosis via mito-ROS-mediated autophagy in COPD, which sheds light on further hazard assessments of MPs on human respiratory health and potential therapeutic agents for patients with COPD.Abbreviations: ADF: autophagy-dependent ferroptosis; AECOPD: acute exacerbation of chronic obstructive pulmonary disease; Cchord: static compliance; COPD: chronic obstructive pulmonary disease; CQ: chloroquine; CS: cigarette smoke; DEGs: differentially expressed genes; Fer-1: ferrostatin-1; FEV 0.1: forced expiratory volume in first 100 ms; FVC: forced vital capacity; GSH: glutathione; HE: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; MDA: malondialdehyde; Mito-ROS: mitochondrial reactive oxygen species; MMA: methyl methacrylate; MMF: maximal mid-expiratory flow curve; MMP: mitochondrial membrane potential; MOI: multiplicity of infection; MPs: microplastics; MV: minute volume; PA: polyamide; PBS: phosphate-buffered saline; PC: polycarbonate; pDHBE: primary human bronchial epithelial cell from COPD patients; PET: polyethylene terephthalate; PIF: peak inspiratory flow; PLA: polylactic acid; pNHBE: primary normal human bronchial epithelial cell; PS-MPs: polystyrene microplastics; PVA: polyvinyl acetate; PVC: polyvinyl chloride; Py-GCMS: pyrolysis gas chromatography mass spectrometry; SEM: scanning electron microscopy; Te: expiratory times; Ti: inspiratory times; TNF/TNF-α: tumor necrosis factor.

SUBMITTER: Wei YY 

PROVIDER: S-EPMC12283003 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature