Polyamines buffer labile iron to suppress ferroptosis

Polyamines act as endogenous buffers of labile iron, restraining its reactivity and thereby suppressing ferroptosis. Depletion of polyamines elevates labile iron levels and creates synthetic lethality with loss of GPX4, a key ferroptosis-suppressing enzyme already under investigation as a cancer therapeutic target. The findings, published in Cell, position polyamine metabolism as a previously unrecognized regulator of iron homeostasis with potential implications for ferroptosis-based anticancer strategies.