Institute of Pathology, University Medical Center Göttingen (UMG), Göttingen, Germany.
Adv Exp Med Biol. 2021;1301:25-40. doi: 10.1007/978-3-030-62026-4_3.
Iron is an ancient, essential and versatile transition metal found in almost all living organisms on Earth. This fundamental trace element is used in the synthesis of heme and iron-sulfur (Fe-S) containing proteins and other vital cofactors that are involved in respiration, redox reactions, catalysis, DNA synthesis and transcription. At the same time, the ability of iron to cycle between its oxidized, ferric (Fe) and its reduced, ferrous (Fe) state contributes to the production of free radicals that can damage biomolecules, including proteins, lipids and DNA. In particular, the regulated non-apoptotic cell death ferroptosis is driven by Fe-dependent lipid peroxidation that can be prevented by iron chelation or genetic inhibition of cellular iron uptake. Therefore, iron homeostasis must be tightly regulated to avoid iron toxicity. This review provides an overview of the origin and chemistry of iron that makes it suitable for a variety of biological functions and addresses how organisms evolved various strategies, including their scavenging and antioxidant machinery, to manage redox-associated drawbacks. Finally, key mechanisms of iron metabolism are highlighted in human diseases and model organisms, underlining the perils of dysfunctional iron handlings.
铁是一种古老、必需且多功能的过渡金属，存在于地球上几乎所有的生物体中。这种基本的痕量元素用于合成血红素和含铁硫（Fe-S）的蛋白质以及其他参与呼吸、氧化还原反应、催化、DNA 合成和转录的重要辅因子。同时，铁在其氧化态（Fe）和还原态（Fe）之间循环的能力导致自由基的产生，自由基可以破坏生物分子，包括蛋白质、脂质和 DNA。特别是，受调控的非凋亡性细胞死亡铁死亡是由 Fe 依赖性脂质过氧化驱动的，可以通过铁螯合或基因抑制细胞铁摄取来预防。因此，铁的动态平衡必须受到严格控制，以避免铁毒性。本文综述了铁的起源和化学性质，这些性质使其适合多种生物学功能，并探讨了生物体如何进化出各种策略，包括其清除和抗氧化机制，来应对与氧化还原相关的缺点。最后，强调了人类疾病和模式生物中铁代谢的关键机制，突出了功能失调的铁处理的危害。
