Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine, McGill University, Montreal, Quebec, Canada.
Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine, McGill University, Montreal, Quebec, Canada.
Mol Aspects Med. 2020 Oct;75:100866. doi: 10.1016/j.mam.2020.100866. Epub 2020 Jun 18.
Iron is a constituent of many metalloproteins involved in vital metabolic functions. While adequate iron supply is critical for health, accumulation of excess iron promotes oxidative stress and causes tissue injury and disease. Therefore, iron homeostasis needs to be tightly controlled. Mammals have developed elegant homeostatic mechanisms at the cellular and systemic level, which serve to satisfy metabolic needs for iron and to minimize the risks posed by iron's toxicity. Cellular iron metabolism is post-transcriptionally controlled by iron regulatory proteins, IRP1 and IRP2, while systemic iron balance is regulated by the iron hormone hepcidin. This review summarizes basic principles of mammalian iron homeostasis at the cellular and systemic level. Particular attention is given on pathways for hepcidin regulation and on crosstalk between cellular and systemic homeostatic mechanisms.
铁是参与重要代谢功能的许多金属蛋白的组成部分。虽然充足的铁供应对健康至关重要，但过量铁的积累会促进氧化应激，导致组织损伤和疾病。因此，铁的动态平衡需要严格控制。哺乳动物在细胞和系统水平上已经发展出了精致的稳态机制，以满足对铁的代谢需求，并将铁毒性带来的风险降到最低。细胞内铁代谢是通过铁调节蛋白 IRP1 和 IRP2 进行转录后调控的，而系统性铁平衡则由铁激素hepcidin 调节。这篇综述总结了哺乳动物在细胞和系统水平上铁稳态的基本原理。特别关注了 hepcidin 调节的途径以及细胞和系统稳态机制之间的串扰。
