Cardiomyocyte hepcidin: From intracellular iron homeostasis to physiological function

Cellular iron is required for the utilization of oxygen in the cell. Iron in iron-sulfur and heme groups is required for electron transfer and oxygen activation in oxidative phosphorylation, while labile free iron is required for oxygen activation by dioxygenases, and as a catalyst for redox signaling. At the same time, this reactivity with oxygen underpins the production of cell-damaging free radicals in the presence of excess iron. Because the cardiac cell is a major site of oxygen flux, it requires tight control of intracellular iron levels. Until recently, such control was thought to be mediated predominantly by the action of iron regulatory proteins. However, new evidence reveals that cardiomyocyte hepcidin is indispensable for the control of intracellular iron levels, normal metabolism and heart function. This new evidence highlights the need for better understanding of the regulation of cardiomyocyte hepcidin in health and disease.