Watt Richard K, Hilton Robert J, Graff D Matthew
Department of Chemistry and Biochemistry, C-100 Benson Building, Brigham Young University, Provo, UT 84602, USA.
Biochim Biophys Acta. 2010 Aug;1800(8):745-59. doi: 10.1016/j.bbagen.2010.03.001. Epub 2010 Mar 7.
Most models for ferritin iron release are based on reduction and chelation of iron. However, newer models showing direct Fe(III) chelation from ferritin have been proposed. Fe(III) chelation reactions are facilitated by gated pores that regulate the opening and closing of the channels.
Results suggest that iron core reduction releases hydroxide and phosphate ions that exit the ferritin interior to compensate for the negative charge of the incoming electrons. Additionally, chloride ions are pumped into ferritin during the reduction process as part of a charge balance reaction. The mechanism of anion import or export is not known but is a natural process because phosphate is a native component of the iron mineral core and non-native anions have been incorporated into ferritin in vitro. Anion transfer across the ferritin protein shell conflicts with spin probe studies showing that anions are not easily incorporated into ferritin. To accommodate both of these observations, ferritin must possess a mechanism that selects specific anions for transport into or out of ferritin. Recently, a gated pore mechanism to open the 3-fold channels was proposed and might explain how anions and chelators can penetrate the protein shell for binding or for direct chelation of iron.
These proposed mechanisms are used to evaluate three in vivo iron release models based on (1) equilibrium between ferritin iron and cytosolic iron, (2) iron release by degradation of ferritin in the lysosome, and (3) metallo-chaperone mediated iron release from ferritin.
大多数铁蛋白铁释放模型基于铁的还原和螯合。然而，已提出了显示从铁蛋白直接螯合Fe(III)的新模型。Fe(III)螯合反应由调节通道开闭的门控孔促进。
结果表明，铁核还原会释放氢氧根离子和磷酸根离子，这些离子从铁蛋白内部排出以补偿进入电子的负电荷。此外，在还原过程中氯离子被泵入铁蛋白，作为电荷平衡反应的一部分。阴离子进出的机制尚不清楚，但这是一个自然过程，因为磷酸盐是铁矿物核心的天然成分，并且非天然阴离子已在体外被纳入铁蛋白。铁蛋白蛋白壳上的阴离子转移与自旋探针研究相矛盾，后者表明阴离子不易纳入铁蛋白。为了兼顾这两种观察结果，铁蛋白必须具备一种机制来选择特定阴离子进出铁蛋白。最近，有人提出了一种打开三重通道的门控孔机制，这可能解释了阴离子和螯合剂如何穿透蛋白壳以结合或直接螯合铁。
这些提出的机制用于评估三种基于以下方面的体内铁释放模型：(1)铁蛋白铁与胞质铁之间的平衡；(2)溶酶体中铁蛋白降解导致的铁释放；(3)金属伴侣介导的铁蛋白铁释放。
