Cellular Iron Metabolism and Regulation
Cellular Iron Metabolism and Regulation
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DOI：
10.1007/978-981-13-9589-5_2
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Chang, Yan-Zhong
中科院分区：
文献类型：
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作者：
Gao, Guofen;Li, Jie;Chang, Yan-Zhong
铁是人体必需的微量元素，但过量的铁是有毒的，因为它有助于氧化损伤。为了使铁浓度保持在最佳的生理范围内，细胞水平和整个系统水平的铁代谢受到严格调节。铁稳态的平衡取决于铁载体、铁转运蛋白和铁调控和储存蛋白的表达水平和活性。肠上皮细胞顶膜上的二价金属转运蛋白1 （DMT1）从饮食中引入非血红素铁，而基膜上的铁转运蛋白1 （FPN1）将铁输出到循环中。然后血浆转铁蛋白（Tf）将铁运送到各种组织和细胞。在与转铁蛋白受体1 （TfR1）结合后，该复合物被内吞进入细胞，铁通过内体膜上的DMT1进入细胞质。游离铁要么在代谢过程中被利用，如血红蛋白和Fe-S簇的合成，要么被隔离在胞质铁蛋白中，作为细胞铁储存。多余的铁可以通过FPN1从细胞中输出。肝源肽hepcidin在控制肠细胞内FPN1水平中起主要调节作用，从而控制全身铁的吸收。在细胞内，铁调节蛋白（IRPs）通过与mrna中的铁反应元件（IRE）结合来调节DMT1、TfR1、铁蛋白和FPN1的表达。hepcidin的释放和IRP-IRE的相互作用都与细胞铁水平的波动相协调。因此，充足和稳定的铁补充是保证身体周围细胞的利用。对细胞铁代谢和调控的分子机制的研究可以推动铁生理学和病理生理学领域的发展。
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 amajor 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.