Fig. 8: MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

Elevated levels of free heme in serum due to hemolysis led to a reduction in MFSD7C expression in AMs and endothelial cells within lung tissue of mice. The decrease of MFSD7C promotes the uptake of fatty acid by CD36. Meanwhile, the downregulation of MFSD7C causes mitochondria dysfunction and dysregulation of ACSL4 and GPX4, which promotes lipid peroxidation and triggers ferroptosis, resulting in hemolytic lung damage. Intravenous administration of MFSD7C mRNA-loaded nanoparticles can restore MFSD7C protein levels, mitigating ferroptosis, and thereby alleviating hemolytic-induced lung damage.