Dysregulated Copper Metabolism-Induced Cuproptosis Contributes to Mitochondrial Dysfunction and Macrophage Inflammatory Response in Acute Lung Injury - PubMed
4 hours ago
- #copper metabolism
- #acute lung injury
- #mitochondrial dysfunction
- Dysregulated copper metabolism and cuproptosis contribute to acute lung injury (ALI).
- RNA-seq data from patients with severe pneumonia showed increased copper metabolism-related gene activity and macrophage enrichment.
- In a mouse ALI model, elevated lung copper levels led to cuproptosis features like DLAT oligomerization and Fe-S protein destabilization.
- Copper chelator tetrathiomolybdate reduced lung injury, inflammation, and cuproptosis markers in vivo.
- LPS challenge in alveolar macrophages increased Cu+ levels, DLAT oligomerization, and impaired Fe-S protein stability.
- Copper chelation or cuproptosis regulator knockdown restored mitochondrial function and reduced inflammatory macrophage polarization.
- The study highlights cuproptosis as a new ALI driver and suggests therapeutic potential of copper homeostasis modulation.