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.
