Journal Article

Regulation of iron acquisition and storage: consequences for iron-linked disorders

Kaplan, Jerry, McVey Ward, Diane, De Domenico, Ivana

2008

Overview

Key Points Iron is essential but toxic. Mammals regulate systemic iron through acquisition and storage. Iron is absorbed in the gut and transported into plasma by an apical divalent metal transporter, DMT1, and a basolateral transporter, ferroportin. Only 1–2 mg of iron is absorbed per day in the gut. Most of the iron in the body is found as haem in red blood cells. Old red blood cells are ingested by macrophages and degraded; iron is then recycled back into plasma by ferroportin. Iron in plasma is carried by the protein transferrin, which provides a chelating environment in plasma and a delivery system to cells that express transferrin receptors. Iron in cells can be used for cellular processes or stored in the cytosolic protein ferritin. Levels of iron transporters, carriers and storage proteins are regulated transcriptionally and post-transcriptionally according to iron status. Hepcidin, a peptide hormone secreted by the liver, is the key molecule that regulates systemic iron metabolism by regulating iron entry into plasma. The transcription of hepcidin is tightly regulated by signalling molecules, which sense iron levels, oxygen levels and inflammation. Hepcidin binds to ferroportin, leading to ferroportin degradation and a consequent decrease in cellular iron export. Iron-overload diseases result from inappropriate iron acquisition in response to iron need. Excess iron can damage tissue, cause fibrosis and give rise to organ failure. Iron-deficiency disorders result in anaemia, which in turn give rise to poor oxygenation of tissue. Insight into the regulation of iron metabolism and iron-related diseases has occurred through genetics and the use of model organisms. Mammalian iron homeostasis is achieved through iron acquisition and storage. Intestinal iron absorption and macrophage-mediated recycling of iron from red blood cells are highly regulated. The discovery of iron transporters and insight into their regulation has provided important information about iron-related disorders. Mammalian iron homeostasis must be meticulously regulated so that this essential element is available for use, but at the same time prevented from promoting the formation of toxic radicals. Controlling the entry of iron into blood plasma is the main mechanism by which iron stores in the body are physiologically manipulated and regulated. Defects in iron acquisition at the cellular and systemic levels lead to human disorders, which involve either iron overload or iron deficiency. Discoveries of iron transporters and insights into their regulation have provided important information about iron metabolism and genetic iron disorders.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biochemistry / Biological Transport - physiology / Biomedical and Life Sciences / Blood / Cancer Research / Carrier proteins / Cell Biology / Control / Developmental Biology / Enzymes / Hemoglobin / Homeostasis / Humans / Iron / Iron - deficiency / Iron - metabolism / Iron metabolism disorders / Iron Metabolism Disorders - genetics / Iron Metabolism Disorders - metabolism / Life Sciences / Mammals / Metabolism / Metabolites / Nutrient deficiency / Physiological aspects / Plasma / Prostheses / review-article / Small intestine / Stem Cells