PerspectiveCell Biology

An Ancient Gauge for Iron

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Science  30 Oct 2009:
Vol. 326, Issue 5953, pp. 676-677
DOI: 10.1126/science.1181938

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Mammalian cells must manage the import, export, and sequestration of iron to achieve the cytosolic concentrations needed to support the synthesis of iron-binding proteins and prevent unfavorable iron-dependent oxidation events. Key to this maintenance are the iron regulatory proteins IRP1 and IRP2, which respond to the cytosolic iron pool by binding to target mRNA and regulating the synthesis of iron metabolism proteins (13). On pages 718 and 722 of this issue, Vashisht et al. and Salahudeen et al. (4, 5) report that human cells gauge cellular iron and concomitantly alter the activity of IRPs through a mechanism that depends on the protein FBXL5. FBXL5 senses iron through an evolutionarily conserved hemerythrin domain that is related to a family of iron- and oxygen-binding proteins in bacteria and invertebrates.