Metabolite buffering of labile iron governs ferroptosis

Polyamines act as endogenous metabolic buffers that reduce the chemical accessibility of labile iron within cells, demonstrating that iron abundance alone does not determine ferroptosis sensitivity. Sharma et al., publishing in Cell, reveal an unexpected function for one of the cell's most abundant metabolite classes and reframe how intracellular iron metabolism is organized. The findings open new avenues for modulating ferroptosis — a regulated cell-death pathway increasingly explored as a therapeutic vulnerability in drug-resistant cancers.