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Polyamines buffer labile iron to suppress ferroptosis

ABSTRACT: Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines function as endogenous buffers of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using genome-wide CRISPR screens, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, GPX4. Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin. To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron. Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution. These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE322913 | GEO | 2026/03/06

REPOSITORIES: GEO

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Polyamines buffer labile iron to suppress ferroptosis

Project description:Polyamines buffer labile iron to suppress ferroptosis

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Polyamines induce the glutamate decarboxylase acid response system by increasing the level of the σ38 subunit (RpoS) of Escherichia coli RNA polymerase via gadE regulon

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