Iron Homeostasis in Health and Disease

Abstract

Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.

Keywords: iron; iron metabolism; iron toxicity.

Figure 1

The importance of Iron in pathophysiologic conditions. Essential to ensure survival, disruption of iron homeostasis has been shown to be involved in a variety of pathophysiological conditions, which include anemia and iron-overload related disorders. In particular, the importance of tissue iron accumulation in inflammation and infection, cancer, genetic, cardiovascular and neurodegenerative diseases continuously increases.