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首页> 外文期刊>Journal of Biophysical Chemistry >Mitochondrial Respiration Is Associated with Alloxan-Induced Mitochondrial Permeability Transition
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Mitochondrial Respiration Is Associated with Alloxan-Induced Mitochondrial Permeability Transition

机译：线粒体呼吸与四氧嘧啶诱导的线粒体通透性转变有关

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We previously showed that increased mitochondrial inner membrane permeability which is known as mitochondrial permeability transition (MPT) is triggered by adding succinate in the presence of the diabetogenic agent alloxan. Here, our aim was to investigate whether mitochondrial respiration is associated with alloxan-induced MPT. After mitochondria isolated from rat liver were incubated with alloxan at 37°C for 5 min, the addition of succinate immediately triggered the MPT in the presence of rotenone. However, little or no induction occurred at incubation temperatures below 25°C. Malate/glutamate also triggered MPT by alloxan in the absence of rotenone. In mitochondrial suspensions containing alloxan, succinate accelerated oxygen consumption that was completely inhibited by cyanide. These results suggest that mitochondrial respiration is associated with the alloxan-induced MPT. Alloxan radical production was investigated using ESR spectroscopy. Mitochondria incubated with succinate and alloxan elicited low signal intensity (radical formation) that increased significantly in the presence of cyanide. When the incubation of alloxan with mitochondria after the addition of succinate, a little intensity of the signal was observed, but it was remarkably increased after the addition of cyanide. Ubiquinone analogues inhibited the MPT induction. These results suggest that the initiation of MPT is associated with alloxan redox cycling via an electron transfer process at a quinone-binding site in respiratory mitochondria.
机译：我们先前显示，通过在糖尿病致病物质四氧嘧啶存在下添加琥珀酸酯，可触发线粒体内膜通透性增加（称为线粒体通透性转变（MPT））。在这里，我们的目的是研究线粒体呼吸是否与四氧嘧啶诱导的MPT有关。从大鼠肝脏分离的线粒体与四氧嘧啶在37°C下孵育5分钟后，在鱼藤酮存在下，琥珀酸的加入立即触发了MPT。但是，在低于25°C的孵育温度下几乎没有诱导。在鱼藤酮不存在的情况下，苹果酸/谷氨酸也被四氧嘧啶触发了MPT。在含有四氧嘧啶的线粒体悬浮液中，琥珀酸酯加速了氧的消耗，而氰化物完全抑制了氧的消耗。这些结果表明线粒体呼吸与四氧嘧啶诱导的MPT有关。使用ESR光谱研究了四氧嘧啶自由基的产生。与琥珀酸盐和四氧嘧啶一起孵育的线粒体引起信号强度低（自由基形成），该信号强度在存在氰化物的情况下显着增加。加入琥珀酸酯后，将四氧嘧啶与线粒体一起孵育时，观察到的信号强度很小，但加入氰化物后，信号强度显着增加。泛醌类似物抑制了MPT的诱导。这些结果表明，MPT的启动与四氧嘧啶氧化还原循环有关，后者通过呼吸线粒体中醌结合位点的电子转移过程进行。

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