Iron metabolism: interactions with normal and disordered erythropoiesis.

Department of Medicine and Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
Cold Spring Harbor perspectives in medicine 05/2012; 2(5):a011668. DOI: 10.1101/cshperspect.a011668
Source: PubMed

ABSTRACT Hemoglobinopathies and other disorders of erythroid cells are often associated with abnormal iron homeostasis. We review the molecular physiology of intracellular and systemic iron regulation, and the interactions between erythropoiesis and iron homeostasis. Finally, we discuss iron disorders that affect erythropoiesis as well as erythroid disorders that cause iron dysregulation.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs) in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5'untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3'untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1 (-/-)/Irp2(-/-) mice), which contrasts with the fact that Irp1 (-/-) and Irp2 (-/-) mice are viable. In addition, Irp2 (-/-) mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1 (-/-) animals were first assessed in the early 1990s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1 (-/-) mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension, and neurodegeneration.
    Frontiers in Pharmacology 01/2014; 5:124.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron is vital for almost all living organisms by participating in a wide range of metabolic processes. However, iron concentration in body tissues must be tightly regulated since excessive iron may lead to microbial infections or cause tissue damage. Disorders of iron metabolism are among the most common human diseases and cover several conditions with varied clinical manifestations. An extensive literature review on the basic aspects of iron metabolism was performed, and the most recent findings on this field were highlighted as well. New insights on iron metabolism have shed light into its real complexity, and its role in both healthy and pathological states has been recognized. Important discoveries about the iron regulatory machine and imbalances in its regulation have been made, which may lead in a near future to the development of new therapeutic strategies against iron disorders. Besides, the toxicity of free iron and its association with several pathologies has been addressed, although it requires further investigations. This review will provide students in the fields of biochemistry and health sciences a brief and clear overview of iron physiology and toxicity, as well as imbalances in the iron homeostasis and associated pathological conditions.
    Journal of Clinical Laboratory Analysis 01/2014; · 1.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. 'Ironomics' certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism.
    06/2014; 41(3):213-21.


Available from