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

Summary

Human COPD lungs contained higher microplastic loads (notably PS-MPs) and iron; PS-MPs induced mito-ROS, lysosome biogenesis/acidification, ferritinophagy, and autophagy-dependent ferroptosis, intensifying inflammation and triggering AECOPD in models. Targeting mito-ROS or ferroptosis attenuated inflammation and exacerbations.

Key Findings

• COPD lung tissues harbored significantly higher levels of microplastics (especially PS-MPs) and iron than controls (Py-GCMS).
• PS-MPs induced mito-ROS, lysosome biogenesis/acidification, ferritinophagy and autophagy-dependent ferroptosis, driving inflammation and AECOPD in vitro and in vivo.
• Mitochondria-targeted ROS scavenging or ferroptosis inhibition reduced inflammation and ameliorated PS-MP–induced AECOPD.

Clinical Implications

Suggests considering ferroptosis-modulating and mito-ROS–targeted strategies in COPD exacerbation management, alongside minimizing microplastic exposure. Supports biomarker development (e.g., iron, ferroptosis signatures) for risk stratification.

Limitations

• Human sample sizes and exposure quantification relative to real-world inhalation are not detailed in the abstract.
• Translational relevance requires clinical validation of ferroptosis-targeted interventions in COPD.

Future Directions

Prospective clinical studies to validate ferroptosis/mito-ROS biomarkers and test ferroptosis-modulating therapies in COPD; environmental interventions to reduce microplastic exposure and assess respiratory benefits.