Recent advances in iron homeostasis and regulation - a focus on epigenetic regulation and stroke.

Iron is an element with redox properties. It is active sites of many enzymes and plays an important role in various cellular and biological functions including ATP production and DNA synthesis. However, as a redox element, iron promotes free radical generation and lipid peroxidation, causing oxidative damage and cell death. Iron-mediated oxidation is a central player in ferroptosis, a type of cell death process that is different from apoptosis and necrosis. Thus, iron metabolism and homeostasis are sophisticatedly regulated. There has been exciting progress in understanding iron metabolism and regulation since hepcidin was recognized as the central regulator of iron homeostasis. Hepcidin mainly regulates the iron export function of the ferrous iron permease, ferroportin, which is the only known iron exporter expressed by mammalian cells. Particularly, epigenetic regulation has been a recent focus on iron homeostasis. Epigenetic phenomena have been demonstrated to modulate key proteins including hepcidin in iron metabolism. Here, we review the rapid progress in recent years in understanding molecular mechanisms of iron homeostasis with a focus on epigenetic regulation of hepcidin, ferritin, and ferroptosis. Interactions between methionine oxidation and iron is also discussed. Furthermore, many studies have suggested that the severity of neuronal damage after stroke is proportional to the magnitude of brain iron accumulation. Recent discoveries regarding iron metabolism in stroke is briefly discussed. Understanding the underlying mechanism in iron regulation could provide insight into the treatment of various intractable diseases including stroke.