Iron sensing and signalling
- 1Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
- 2Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Medical University of Vienna, Vienna, Austria
- Correspondence to Professor Christoph Gasche, AKH Wien, KIM3, Gastroenterologie, Währinger Gürtel 18–20, A1090 Vienna, Austria;
Iron deficiency is a common condition increasingly diagnosed and treated by gastroenterologists. The most common presentation of iron deficiency is anaemia; however, it is a systemic disorder affecting multiple aspects of health in various organs. Iron is an essential element, with iron-containing proteins exerting a variety of vital functions, including oxygen transport, cellular respiration, intermediary metabolism, regulation of transcription and DNA repair. Major pathways of iron utilisation and production of iron-containing proteins include iron sulphur cluster biosynthesis, haem synthesis and storage within ferritin. The main site of iron absorption is the small intestine, but most iron is recycled by the monocyte–macrophage system via phagocytosis of senescent erythrocytes. Hepcidin, the key iron-regulating peptide binds to the iron exporter ferroportin and leads to its degradation, thereby inhibiting intestinal iron absorption and cellular export. Hepcidin levels are regulated on a transcriptional level by various stimuli, including transferrin saturation, erythropoietic activity, hypoxia and inflammation. Iron deficiency evokes adaptive responses resulting in alteration of cellular metabolism, changes in gene expression, activation of signalling pathways, cell cycle regulation, differentiation and cell death. Such responses are mediated by a number of iron-sensitive signalling pathways, including the IRE/IRP system, HIF and haem signalling. This review provides a molecular perspective for the clinician and highlights important biological aspects of iron deficiency.
Funding This study was funded by Austrian Science Funds (FWF P21200) and the Christian Doppler Research Association. The financial support of the Federal Ministry of Economy, Family and Youth and the National Foundation for Research, Technology and Development is gratefully acknowledged.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.