Cells require a constant source of iron, which serves as a functional component of hemoproteins and iron-sulfur (Fe-S) cluster-containing proteins. The acquisition of iron by cells is critical for survival, growth and differentiation ( Andrews, 2008). Our results reveal features of intracellular iron homeostasis that are conserved from bacteria through humans. Siderophore-depleted mammalian cells and zebrafish embryos fail to synthesize heme, an iron-dependent mitochondrial process. Mammalian cells lacking the siderophore accumulate abnormally high amounts of cytoplasmic iron, resulting in elevated levels of reactive oxygen species, whereas the mitochondria are iron deficient. RNA interference-mediated knockdown of the murine homologue of EntA results in siderophore depletion. We find that the murine enzyme responsible for 2,5-DHBA synthesis is the homologue of bacterial EntA, which catalyzes 2,3-DHBA production during enterobactin biosynthesis.
Here we show that the iron-binding moiety of the 24p3-associated mammalian siderophore is 2,5-dihydroxybenzoic acid (2,5-DHBA), which is similar to 2,3-DHBA, the iron-binding component of enterobactin.
Lipocalin 24p3 is an iron trafficking protein that binds iron through association with a bacterial siderophore, such as enterobactin, or a postulated mammalian siderophore. Intracellular iron homeostasis is critical for survival and proliferation.
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