Sone N, Larsstuvold M K, Kagawa Y
J Biochem. 1977 Sep;82(3):859-68. doi: 10.1093/oxfordjournals.jbchem.a131762.
the toxic effects of CH3HgCL on mitochondria of mammalian organs including human and rat liver were examined. [203Hg]CH3HGCl was bound mainly to mitochondrial proteins. The binding was not effected by the energy state of mitochondria. The state 3 respiration, oxidative phosphorylation and 32Pi-ATP exchange reaction were inhibited by 10 to 50 nmol of CH3HgCl per mg of mitochondrial protein, while NADH-and succinate-dehydrogenase and ATPase were more resistant to it The difference spectrum of the treated mitochondria indicated that the point of inhibition was located after flavin and before cytochrome b. Mitochondrial swelling was induced by CH3HgCl, in accordance with previous morphological observations in vivo. The swelling, stimulation of ATPase and energy-dependent H+ extrusion cauded by CH3HgCl were equally dependent on K+. Under these conditions, uptake of K+ by mitochondria was increased and the membrane potential was dissipated. Unlike the case with other organomercuric compounds, transport of phosphate was not inhibited by CH3HgCl. When tested on liposomes, CH3HgCl itself was not lipid-soluble, as some organomercuric compounds are, and was not an uncoupler or a K+-carrier. It was concluded that protein bound CH3HgS-induced K+ uptake into mitochondria and the resulting loss of membrane potential was the major cause of uncoupling, though at higher concentrations, the electron transport system was also inhibited.
研究了氯化甲基汞（CH3HgCL）对包括人和大鼠肝脏在内的哺乳动物器官线粒体的毒性作用。[203Hg]CH3HGCl主要与线粒体蛋白结合。这种结合不受线粒体能量状态的影响。每毫克线粒体蛋白中10至50纳摩尔的CH3HgCl可抑制状态3呼吸、氧化磷酸化和32Pi-ATP交换反应，而NADH和琥珀酸脱氢酶以及ATP酶对其更具抗性。处理后线粒体的差示光谱表明，抑制点位于黄素之后、细胞色素b之前。根据先前在体内的形态学观察，CH3HgCl可诱导线粒体肿胀。CH3HgCl引起的肿胀、ATP酶的刺激和能量依赖性H+外流同样依赖于K+。在这些条件下，线粒体对K+的摄取增加，膜电位消散。与其他有机汞化合物不同，CH3HgCl不抑制磷酸盐的转运。在脂质体上进行测试时，CH3HgCl本身不像某些有机汞化合物那样具有脂溶性，也不是解偶联剂或K+载体。得出的结论是，蛋白质结合的CH3HgS诱导线粒体摄取K+并导致膜电位丧失是解偶联的主要原因，尽管在较高浓度下，电子传递系统也会受到抑制。
