Tong Wing-Hang, Rouault Tracey A
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, NIH Bldg 18, Rm 101, Bethesda, MD 20892, USA.
Biometals. 2007 Jun;20(3-4):549-64. doi: 10.1007/s10534-006-9047-6. Epub 2007 Jan 5.
Iron and citrate are essential for the metabolism of most organisms, and regulation of iron and citrate biology at both the cellular and systemic levels is critical for normal physiology and survival. Mitochondrial and cytosolic aconitases catalyze the interconversion of citrate and isocitrate, and aconitase activities are affected by iron levels, oxidative stress and by the status of the Fe-S cluster biogenesis apparatus. Assembly and disassembly of Fe-S clusters is a key process not only in regulating the enzymatic activity of mitochondrial aconitase in the citric acid cycle, but also in controlling the iron sensing and RNA binding activities of cytosolic aconitase (also known as iron regulatory protein IRP1). This review discusses the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe-S cluster biogenesis regulate the Fe-S cluster switch and modulate intracellular citrate flux.
铁和柠檬酸对大多数生物体的新陈代谢至关重要，在细胞和全身水平上对铁和柠檬酸生物学的调节对于正常生理功能和生存至关重要。线粒体和胞质乌头酸酶催化柠檬酸和异柠檬酸的相互转化，乌头酸酶的活性受铁水平、氧化应激以及铁硫簇生物合成装置状态的影响。铁硫簇的组装和拆卸不仅是调节柠檬酸循环中线粒体乌头酸酶酶活性的关键过程，也是控制胞质乌头酸酶（也称为铁调节蛋白IRP1）的铁感应和RNA结合活性的关键过程。本综述讨论了乌头酸酶在中间代谢中的核心作用，并探讨了铁稳态和铁硫簇生物合成如何调节铁硫簇开关并调节细胞内柠檬酸通量。
