Drapier J C
U 365 Inserm, Section de Recherche, Institut Curie, Paris, France.
Methods. 1997 Mar;11(3):319-29. doi: 10.1006/meth.1996.0426.
In mammalian cells, nitric oxide (NO) synthesis results in the inactivation of several mitochondrial iron-sulfur enzymes involved in ATP synthesis that correlates with the appearance of complexes of the [(NO)2Fe(SR)2] type detectable by electron paramagnetic resonance spectroscopy. More specifically, the activity of two [Fe-S] enzymes was followed during the course of NO synthase expression:mitochondrial aconitase, which catalyzes citrate:isocitrate conversion in the Krebs cycle, and cytoplasmic aconitase, or iron regulatory protein (IRP), a trans-regulator that controls expression at the posttranscriptional level of proteins involved in iron metabolism. In response to physiological stimuli, the synthesis of NO leads to inhibition of enzymatic activities of both mitochondrial and cytoplasmic aconitases, whereas the RNA binding activity of IRP is increased. Coordination of the diffusible gas NO with [Fe-S] clusters is thought to result in impairment of metabolic functions. Here it is proposed that the interplay between NO (or some NO-derived molecule) and [Fe-S] clusters at critical catalytic or allosteric sites is crucial in the response to environmental signals within cells.
在哺乳动物细胞中，一氧化氮（NO）的合成会导致几种参与ATP合成的线粒体铁硫酶失活，这与通过电子顺磁共振光谱可检测到的[(NO)2Fe(SR)2]类型复合物的出现相关。更具体地说，在一氧化氮合酶表达过程中跟踪了两种[Fe-S]酶的活性：线粒体乌头酸酶，它催化三羧酸循环中柠檬酸向异柠檬酸的转化；以及细胞质乌头酸酶，即铁调节蛋白（IRP），一种在转录后水平控制参与铁代谢的蛋白质表达的反式调节因子。响应生理刺激时，NO的合成会导致线粒体和细胞质乌头酸酶的酶活性均受到抑制，而IRP的RNA结合活性则会增加。人们认为可扩散气体NO与[Fe-S]簇的配位会导致代谢功能受损。本文提出，在关键催化或变构位点处，NO（或某些NO衍生分子）与[Fe-S]簇之间的相互作用对于细胞内对环境信号的响应至关重要。
