Superoxides from mitochondrial complex III: The role of manganese superoxide dismutase
Superoxides from mitochondrial complex III: The role of manganese superoxide dismutase
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DOI：
10.1016/s0891-5849(00)00338-5
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发表时间：
2000-07-15
影响因子：
7.4
通讯作者：
Robinson, BH
中科院分区：
文献类型：
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作者：
Raha, S;McEachern, GE;Robinson, BH
在本报告中，我们用化学发光探针coelenterazine测量到，当抗霉素A抑制大鼠心肌线粒体的泛醌细胞色素C还原酶(复合体III)时，它产生大量的超氧化物。当线粒体被Myxthiiazol或Ismatellin抑制时，没有检测到超氧化物的形成。使用霉菌唑或豆蔻菌素可以显著减少抗霉素A敏感自由基的产生。这表明，抗霉素A敏感的超氧化物的产生主要来自Q(O)半泛醌。当锰超氧化物歧化酶耗竭的亚线粒体颗粒(SMP)被霉菌素或豆蔻素抑制时，观察到一个大的超氧化物信号。这两种抑制剂可能会增加Q(I)半喹酮在N中心的浓度。在线粒体和SMP的情况下，抗霉素A敏感的信号可以通过添加铜锌超氧化物歧化酶而消散，这表明所测量的腔肠净信号是超氧化物产生的结果。综上所述，这些数据表明，在完整的线粒体中，MnSOD能更有效地清除Q(I)物种产生的自由基。(C)2000年爱思唯尔科学公司。
In this report we show that ubiquinone cytochrome c reductase (complex III) from isolated rat heart mitochondria when inhibited with antimycin A, produces a large amount of superoxide as measured by the chemiluminescent probe coelenterazine. When mitochondria are inhibited with myxothiazol or stigmatellin, there is no detectable formation of superoxide. The antimycin A-sensitive free radical production can be dramatically reduced using either myxothiazol or stigmatellin. This suggests that the antimycin A-sensitive generation of superoxides originates primarily from the Q(o) semiubiquinone. When manganese superoxide dismutase depleted submitochondrial particles (SMP) were inhibited with myxothiazol or stigmatellin, a large superoxide signal was observed. These two inhibitors likely increase the concentration of the Q(i) semiquinone at the N center. The antimycin A-sensitive signal can, in the case of both the mitochondria and the SMP, be dissipated by the addition of copper zinc superoxide dismutase, suggesting that the measured coelenterazine signal was a result of superoxide production. Taken together, this data suggests that free radicals generated from the Q(i) species are more effectively eliminated by MnSOD in intact mitochondria. (C) 2000 Elsevier Science Inc.