动物血红素运输通路的研究进展

Unravelling the Mechanisms of Cellular Heme Trafficking in Animals

血红素作为一种含铁卟啉化合物,是血红蛋白、细胞色素、过氧化氢酶、过氧化物酶等众多蛋白质的辅基。绝大多数动物自身能够合成血红素,供给氧气运输、电子传递、信号转导等代谢活动,多余的血红素由血红素加氧酶降解。此外,动物体内存在特定的分子通路,负责血红素的吸收、外排、利用及其在细胞间和组织间的转运。近年来,研究人员利用小鼠、秀丽隐杆线虫(Caenorhabditis elegans)等模式动物,发现了猫白血病病毒C亚型受体(feline leukemia virus subgroup C receptor,FLVCR)、血红素感应基因-1(heme responsive gene-1,HRG-1)等多个血红素转运蛋白,同时还建立了一系列感应和检测细胞内血红素的技术。这些研究有力地推动了对血红素运输通路的认识,对深入了解细胞物质运输及机体生命代谢具有重要意义。该文综述了动物细胞血红素运输机制的研究进展,总结了近年来出现的血红素研究技术方法并对热点问题和研究方向进行了探讨。

Hemes are a class of porphyrin cofactors that are required for the function of many proteins including hemoglobin, cytochromes, catalases, and peroxidases. Most animals can use glycine, succinyl Co A, and ferrous iron as substrates to synthesize heme, while excess heme is degraded by heme oxygenases. Cellular and organismal heme homeostasis in animals is also maintained by specific trafficking pathways. In recent years, studies using mouse and worm as the genetic models have led to the discovery of a number of heme transporters including FLVCR and HRG-1. These studies, together with the development of new tools to sense and detect heme, have significantly advanced the fundamental understanding of heme homeostasis, cellular transport, and cell metabolism. This review summarizes recent progresses on heme trafficking, with emphasis on the molecular mechanisms and research methodology.