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Iron mineralization and core dissociation in mammalian homopolymeric H-ferritin: Current understanding and future perspectives.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-08-14 , DOI: 10.1016/j.bbagen.2020.129700
Artem Melman 1 , Fadi Bou-Abdallah 2
Affiliation  

Background

The mechanism of iron oxidation and core formation in homopolymeric H-type ferritins has been extensively studied in-vitro, so has the reductive mobilization of iron from the inorganic iron(III) core. However, neither process is well-understood in-vivo despite recent scientific advances.

Scope of review

Here, we provide a summary of our current understanding of iron mineralization and iron core dissolution in homopolymeric H-type ferritins and highlight areas of interest and further studies that could answer some of the outstanding questions of iron metabolism.

Major conclusions

The overall iron oxidation mechanism in homopolymeric H-type ferritins from vertebrates (i.e. human H and frog M ferritins) is similar, despite nuances in the individual oxidation steps due to differences in the iron ligand environments inside the three fold channels, and at the dinuclear ferroxidase centers. Ferrous cations enter the protein shell through hydrophilic channels, followed by their rapid oxidization at di‑iron centers. Hydrogen peroxide produced during iron oxidation can react with additional iron(II) at ferroxidase centers, or at separate sites, or possibly on the surface of the mineral core. In-vitro ferritin iron mobilization can be achieved using a variety of reducing agents, but in-vivo iron retrieval may occur through a variety of processes, including proteolytic degradation, auxiliary iron mobilization mechanisms involving physiological reducing agents, and/or oxidoreductases.

General significance

This review provides important insights into the mechanisms of iron oxidation and mobilization in homopolymeric H-type ferritins, and different strategies in maintaining iron homeostasis.



中文翻译:

哺乳动物均聚H-铁蛋白中的铁矿化和核心解离:当前的理解和未来的观点。

背景

均已在体外广泛研究了均聚H型铁蛋白中铁的氧化和铁心形成的机理,因此铁从无机铁(III)核中的还原动员也得到了广泛的研究。但是,尽管最近有科学进展,但两种方法在体内均未得到很好的理解。

审查范围

在这里,我们提供了我们对铁矿化和铁芯在均聚H型铁蛋白中的溶解的当前理解的总结,并重点介绍了感兴趣的领域和进一步的研究,这些研究可以回答铁代谢的一些突出问题。

主要结论

脊椎动物的均聚物H型铁蛋白(即人H和青蛙M铁蛋白)的总体铁氧化机理是相似的,尽管由于三折通道内和双核中铁配体环境的差异,单个氧化步骤存在细微差别。亚铁氧化酶中心。亚铁阳离子通过亲水通道进入蛋白质壳,然后在双铁中心迅速被氧化。铁氧化过程中产生的过氧化氢可与其他氧化铁在二氧化亚铁酶中心,或在单独的位置,或可能在矿物芯的表面上反应。可以使用多种还原剂实现铁蛋白的体外动员,但体内铁的回收可能通过多种过程发生,包括蛋白水解降解,

一般意义

这篇综述提供了有关均聚H型铁蛋白中铁氧化和动员的机制的重要见解,以及维持铁稳态的不同策略。

更新日期:2020-08-18
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