Liu Xiaofeng, Theil Elizabeth C
CeBIC (Center for BioIron at CHORI, The Children's Hospital Oakland Research Institute), Oakland, California 94609, USA.
Ann N Y Acad Sci. 2005;1054:136-40. doi: 10.1196/annals.1345.016.
Ferritin has a broad role to play in new strategies for managing Cooley's anemia and the thalassemias. Serum ferritin iron content is relegated to reporting on tissue iron concentrations. Recently, a new property of ferritin was discovered: gated pores, which are highly conserved in ferritins of humans down to bacteria, and control iron flow to chelators. The pore gates can be selectively opened to increase chelator access by mutation, temperature, and physiological concentrations of urea. In another recent observation, the iron in ferritin from seeds such as soybeans has been shown to be readily available to tissues with high demand for iron, such as red blood cells, but slower to be mobilized in other tissues, compared to nonheme iron salts, presumably through a controlled iron gating mechanism. Because the iron pore gating property of ferritin is more thoroughly investigated, and the knowledge that much of the iron to be chelated in the thalassemias is from a solid iron mineral inside the ferritin protein nanocage, a new role of ferritin in regulating cellular iron homeostasis is established. Two new areas, based on recent knowledge of the molecular properties of ferritin, are (1) exploration of food ferritin as a potentially safer form of dietary nonheme iron, and (2) development of chelators targeted to ferritin protein pores that control chelator access.
铁蛋白在治疗库利贫血和地中海贫血的新策略中发挥着广泛作用。血清铁蛋白铁含量用于报告组织铁浓度。最近，人们发现了铁蛋白的一种新特性：门控孔，这种孔在从人类到细菌的铁蛋白中高度保守，可控制铁向螯合剂的流动。通过突变、温度和生理浓度的尿素可选择性地打开孔门，以增加螯合剂的可及性。在另一项近期观察中，已表明大豆等种子中的铁蛋白所含的铁很容易被对铁需求量大的组织（如红细胞）获取，但与非血红素铁盐相比，在其他组织中其铁的动员速度较慢，这可能是通过一种受控的铁门控机制实现的。由于对铁蛋白的铁孔门控特性进行了更深入的研究，并且了解到地中海贫血中许多要螯合的铁来自铁蛋白蛋白质纳米笼内的固态铁矿物，因此确立了铁蛋白在调节细胞铁稳态中的新作用。基于对铁蛋白分子特性的最新认识，有两个新领域：（1）探索食物铁蛋白作为一种潜在更安全的膳食非血红素铁形式；（2）开发针对铁蛋白蛋白质孔的螯合剂，以控制螯合剂的可及性。
