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Vitam Horm. 2017;105:143-160. doi: 10.1016/bs.vh.2017.01.001. Epub 2017 Mar 15.

Mutual Cross Talk Between Iron Homeostasis and Erythropoiesis.

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University of Milan, Milano, Italy.
University of Milan, Milano, Italy. Electronic address:


Iron is necessary for physiological processes essential for the activity of all cells, but the erythropoietic compartment is a privileged iron consumer. In fact, a considerable amount of iron is daily required for hemoglobin synthesis and erythroid cell proliferation. Therefore, a tight link exists between iron metabolism and erythropoiesis. The iron needed for hemoglobin synthesis is mainly ensured by inhibiting hepcidin expression, thereby increasing both ferroportin-mediated iron export from the duodenal absorptive cells and iron release from the reticuloendothelial cells that process old and/or damaged red blood cells. This mechanism makes certain that sufficient iron availability to the erythropoietic compartment occurs. Recent studies established that hypoxia and/or hypoxia-induced erythropoietin are not direct regulators of hepcidin, which is indirectly inhibited by erythropoietic drive, in particular under pathological conditions characterized by expanded but ineffective erythropoiesis, such as β-thalassemia. Among the number of factors proposed as mediators linking erythropoiesis with liver hepcidin suppression, erythroferrone, a hormone produced and secreted by erythroid precursors, appears the best candidate.


Erythroferrone; Erythropoiesis; Hepcidin; Iron

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