Cell·· 22 hours agoPickScore83
Perforin triggers iron-induced mitochondrial damage to drive ferroptosis and anti-tumor immunity.
In brief
Prf1 can directly induce ferroptosis in tumor cells independently of granzymes. Its pore-forming activity drives transferrin receptor endocytosis and iron uptake, and promotes endosomal-mitochondrial contacts, causing mitochondrial iron accumulation and dysfunction. In murine tumor models, dietary iron supplementation suppressed tumor progression in a Prf1-dependent manner, and higher Prf1 expression in cancer patients correlated with improved survival and enhanced response to immune checkpoint blockade.
Why it matters
Links Prf1's direct killing to ferroptosis and identifies transferrin receptor-mediated iron uptake, endosomal-mitochondrial contacts, and mitochondrial iron accumulation.
Source: Cell · doi.org