Erythropoietin and iron-a conflicted alliance?

Suzuki et al. analyzed a mouse model of erythropoietin-deficient anemia to show that during iron overload renal interstitial fibroblasts accumulate iron, and this impairs the hypoxia-driven transcription of the erythropoietin gene. The authors show that excess iron decreases levels of hypoxia-inducible transcription factor 2α (HIF2α), the main driver of erythropoietin production in hypoxia and anemia. The work advances our understanding of the effect of iron on hypoxia signaling, but its implications for anemia treatment are less clear.