Cell-to-cell transfer of damaged mitochondria as a target to reduce lung development problems caused by moderate high oxygen in bronchopulmonary dysplasia

Fibroblasts exhibited a disease-associated phenotype under 60% oxygen, influencing type II alveolar epithelial cells in a model of bronchopulmonary dysplasia.

• Single-cell RNA sequencing revealed that fibroblasts transitioned toward a disease-associated phenotype in high oxygen conditions.
• Enhanced communication between fibroblasts and type II alveolar epithelial cells was observed under moderate hyperoxia.
• Activated fibroblasts increased the vulnerability of type II alveolar epithelial cells to hyperoxia through the release of extracellular vesicles.
• Extracellular vesicles from fibroblasts contained mitochondrial components, particularly the outer mitochondrial membrane protein VDAC1.
• These vesicles inhibited the initiation of mitophagy in type II alveolar epithelial cells, resulting in impaired mitochondrial function.
• Blocking fibroblast-derived extracellular vesicle release improved type II alveolar epithelial cell function and reduced structural damage.

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