Control of systemic iron homeostasis by the hemojuvelin-hepcidin axis

Systemic iron homeostasis is maintained by the coordinate regulation of iron absorption in the duodenum, iron recycling of senescent erythrocytes in macrophages, and mobilization of storage iron in the liver. These processes are controlled by hepcidin, a key iron regulatory hormone. Hepcidin is a 25-amino acid peptide secreted predominantly from hepatocytes. It downregulates ferroportin, the only known iron exporter, and therefore inhibits iron efflux from duodenal enterocytes, macrophages, and hepatocytes into the circulation. Hepcidin expression is regulated positively by body iron load. Although the underlying mechanism of iron-regulated hepcidin expression has not been fully elucidated, several proteins have been identified that participate in this process. Among them, hemojuvelin (HJV) plays a particularly important role. HJV undergoes complicated post-translational processing in an iron-dependent manner, and it interacts with multiple proteins that are essential for iron homeostasis. In this review, I focus on the recent findings that elucidate the role of HJV and its interacting partners in the modulation of hepatic hepcidin expression.