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Linking hypoxia and iron homeostasis: a ‘plate’ full of factors
  1. V Nathan Subramaniam,
  2. Daniel F Wallace
  1. Membrane Transport Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  1. Correspondence to Professor V Nathan Subramaniam, Membrane Transport Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia; Nathan.Subramaniam{at}qimrberghofer.edu.au

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Hepcidin, a 25-amino acid peptide expressed almost exclusively in the liver, is the central regulator of systemic body iron homeostasis. Since its initial identification and characterisation as an antimicrobial peptide, it has become clear that hepcidin plays a role in many metabolic processes. Mutations in hepcidin lead to one form of the severe iron overload disorder juvenile haemochromatosis (type 2B). Hepcidin is a negative regulator of iron absorption and recycling; under normal conditions, increased iron in the body results in an enhanced secretion of hepcidin by the liver, the central organ responsible for iron regulation. Hepcidin then binds the iron transporter ferroportin, inducing its internalisation and degradation, thus reducing iron absorption by enterocytes of the duodenum, and iron recycling by macrophages.1 Hepcidin itself is also regulated by other factors besides iron levels; these include hypoxia, erythropoietic activity, proinflammatory cytokines and other hormones.2 These factors thus work to either increase or decrease iron availability as required.

Hypoxia, the inadequate availability of oxygen, is inextricably linked to the oxygenation levels in blood and occurs in a number of situations including high altitude conditions. The oxygenation of blood in turn is directly linked to the proteins myoglobin, a component of muscle, and haemoglobin, an essential constituent of red blood cells, and the amount of oxygen transported by these molecules. Under hypoxic conditions, the normal response of the organism is to increase the number of red blood cells, thereby increasing the delivery of oxygen to starved tissues and organs. Under hypoxic conditions, the signalling pathway involving hypoxia inducible factors (HIFs) is activated. This results in …

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