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New insights into iron regulation and erythropoiesis

Kim, Airie; Nemeth, Elizabeta

Current Opinion in Hematology: May 2015 - Volume 22 - Issue 3 - p 199–205
doi: 10.1097/MOH.0000000000000132
Editor's Choice

Purpose of review Iron homeostasis and erythropoiesis regulate each other to ensure optimal delivery of oxygen and iron to cells and tissues. Defining the mechanisms of this crosstalk is important for understanding the pathogenesis of common conditions associated with disordered iron metabolism and erythropoiesis.

Recent findings Stress erythropoiesis causes suppression of hepcidin to increase iron availability for hemoglobin synthesis. The erythroid hormone erythroferrone (ERFE) was identified as the mediator of this process. ERFE and additional candidates (TWSG1 and GDF15) may also mediate hepcidin suppression in ineffective erythropoiesis. Several mechanisms by which iron regulates erythropoiesis were also recently identified. Iron deficiency suppresses erythropoietin production via the IRP1–HIF2α axis to prevent excessive iron usage by erythropoiesis during systemic iron restriction. Iron restriction also directly impairs erythroid maturation by inhibiting aconitase, and this can be reversed by the administration of the aconitase product isocitrate. Another novel target is GDF11, which is thought to autoinhibit erythroid maturation. GDF11 traps show promising pharmacologic activity in models of both ineffective erythropoiesis and iron-restricted anemia.

Summary This review summarizes exciting advances in understanding the mechanisms of iron and erythropoietic regulation, and development of novel therapeutic tools for disorders resulting from dysregulation of iron metabolism or erythropoiesis.

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA

Correspondence to Elizabeta Nemeth, PhD, UCLA, Department of Medicine, David Geffen School of Medicine, University of California, 10833 LeConte Ave, CHS 37-131, Los Angeles, CA 90095, USA. Tel: +1 310-825-7499; e-mail:

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