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Cellular Iron Metabolism and Regulation

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Brain Iron Metabolism and CNS Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1173))

Abstract

Iron is an essential trace element in the human body, but excess iron is toxic as it contributes to oxidative damage. To keep iron concentration within the optimal physiologic range, iron metabolism at the cellular level and the whole systemic level are tightly regulated. Balance of iron homeostasis depends on the expression levels and activities of iron carriers, iron transporters, and iron regulatory and storage proteins. Divalent metal transporter 1 (DMT1) at the apical membrane of intestinal enterocyte brings in non-heme iron from the diet, whereas ferroportin 1 (FPN1) at the basal membrane exports iron into the circulation. Plasma transferrin (Tf) then carries iron to various tissues and cells. After binding to transferrin receptor 1 (TfR1), the complex is endocytosed into the cell, where iron enters the cytoplasm via DMT1 on the endosomal membrane. Free iron is either utilized in metabolic processes, such as synthesis of hemoglobin and Fe–S cluster, or sequestered in the cytosolic ferritin, serving as a cellular iron store. Excess iron can be exported from the cell via FPN1. The liver-derived peptide hepcidin plays a major regulatory role in controlling FPN1 level in the enterocyte, and thus controls the whole-body iron absorption. Inside the cells, iron regulatory proteins (IRPs) modulate the expressions of DMT1, TfR1, ferritin, and FPN1 via binding to the iron-responsive element (IRE) in their mRNAs. Both the release of hepcidin and the IRP–IRE interaction are coordinated with the fluctuation of the cellular iron level. Therefore, an adequate and steady iron supplement is warranted for the utilization of cells around the body. Investigations on the molecular mechanisms of cellular iron metabolism and regulation could advance the fields of iron physiology and pathophysiology.

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Authors and Affiliations

  1. Laboratory of Molecular Iron Metabolism, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei Province, China

    Guofen Gao, Jie Li, Yating Zhang & Yan-Zhong Chang

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  1. Guofen Gao
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  2. Jie Li
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  3. Yating Zhang
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  4. Yan-Zhong Chang
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Correspondence to Guofen Gao or Yan-Zhong Chang .

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  1. College of Life Sciences, Hebei Normal University , Shijiazhuang, Hebei, China

    Yan-Zhong Chang

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Gao, G., Li, J., Zhang, Y., Chang, YZ. (2019). Cellular Iron Metabolism and Regulation. In: Chang, YZ. (eds) Brain Iron Metabolism and CNS Diseases. Advances in Experimental Medicine and Biology, vol 1173. Springer, Singapore. https://doi.org/10.1007/978-981-13-9589-5_2

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