Two to Tango: Regulation of Mammalian Iron Metabolism

European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell (Impact Factor: 32.24). 07/2010; 142(1):24-38. DOI: 10.1016/j.cell.2010.06.028
Source: PubMed


Disruptions in iron homeostasis from both iron deficiency and overload account for some of the most common human diseases. Iron metabolism is balanced by two regulatory systems, one that functions systemically and relies on the hormone hepcidin and the iron exporter ferroportin, and another that predominantly controls cellular iron metabolism through iron-regulatory proteins that bind iron-responsive elements in regulated messenger RNAs. We describe how the two distinct systems function and how they "tango" together in a coordinated manner. We also highlight some of the current questions in mammalian iron metabolism and discuss therapeutic opportunities arising from a better understanding of the underlying biological principles.

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Available from: Clara Camaschella, Aug 25, 2014
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    • "The expression of hepcidin (encoded by the HAMP gene) is regulated by iron stores, inflammation, hypoxia, and erythropoiesis, processes that are regulated primarily by the BMP/SMAD and JAK/STAT signaling pathways[5] [6]. Many iron-related disorders are associated with altered hepcidin expression[7]. "

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    • "The regulation of iron metabolism may be divided into two levels: systemic (distribution of iron among the various tissues of the body) and intracellular. Iron entering a cell is either used for biosynthetic reactions or the unused iron is stored in the cytoplasm or in the mitochondria in the form of ferritin or mitoferrin, or can leave the cell (Hentze et al., 2010). The iron metabolism of the body is orchestrated by hepcidin, the only known iron regulatory hormone (Park et al., 2001). "
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    ABSTRACT: A number of pathophysiological conditions are related to iron metabolism disturbances. Some of them are well known, others are newly discovered or special. Hepcidin is a newly identified iron metabolism regulating hormone which could be a promising biomarker for many disorders. In this review we provide background information about mammalian iron metabolism, cellular iron trafficking and the regulation of expression of hepcidin. Beside these molecular biological processes we summarize the methods which have been used to determine blood and urine hepcidin levels and present those pathological conditions (cancer, inflammation, neurological disorders) when hepcidin measurement may have clinical relevance. This article is protected by copyright. All rights reserved.
    Cell Biology International 06/2015; 39(11). DOI:10.1002/cbin.10505 · 1.93 Impact Factor
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    • "Indeed, the redox cycling of ferrous and ferric iron in the physiological presence of H 2 O 2 in the cells results in the formation of reactive oxygen intermediates/free radicals (such as hydroxyl radicals) via the Fenton reaction which in turn can damage lipids, DNA, proteins, and other cellular components. Therefore, regulatory interactions between host iron homeostasis (quantity and subcellular location) and immune function are crucial, since both iron deficiency and iron excess can compromise cellular functions [3]. Access to iron is particularly important in the context of host-pathogen interactions. "
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    ABSTRACT: African trypanosomosis is a chronic debilitating disease affecting the health and economic well-being of developing countries. The immune response during African trypanosome infection consisting of a strong proinflammatory M1-type activation of the myeloid phagocyte system (MYPS) results in iron deprivation for these extracellular parasites. Yet, the persistence of M1-type MYPS activation causes the development of anemia (anemia of chronic disease, ACD) as a most prominent pathological parameter in the mammalian host, due to enhanced erythrophagocytosis and retention of iron within the MYPS thereby depriving iron for erythropoiesis. In this review we give an overview of how parasites acquire iron from the host and how iron modulation of the host MYPS affects trypanosomosis-associated anemia development. Finally, we also discuss different strategies at the level of both the host and the parasite that can/might be used to modulate iron availability during African trypanosome infections.
    06/2015; 2015:1-15. DOI:10.1155/2015/819389
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