UBISEMIQUINONE IS THE ELECTRON-DONOR FOR SUPEROXIDE FORMATION BY COMPLEX III OF HEART-MITOCHONDRIA

UBISEMIQUINONE IS THE ELECTRON-DONOR FOR SUPEROXIDE FORMATION BY COMPLEX III OF HEART-MITOCHONDRIA
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DOI:
10.1016/0003-9861(85)90293-0
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发表时间:
1985-01-01
影响因子:
3.9
通讯作者:
LEHNINGER, AL
LEHNINGER, AL
中科院分区:
生物学3区
文献类型:
--
作者:
TURRENS, JF;ALEXANDRE, A;LEHNINGER, AL

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许多证据表明,超氧化物是在氰化物敏感反应中由 O2 产生的,涉及线粒体呼吸链复合物 III 的还原成分,特别是当存在抗霉素 A 时。尽管人们普遍认为泛半醌是 O2 的电子供体,但支持这一观点的实验证据却很少报道。在完整的大鼠心脏线粒体中,在抗霉素 A 存在下,用琥珀酸盐作为电子供体进行实验,该线粒体含有大量超氧化物歧化酶,但含有少量过氧化氢酶,结果表明,myxothiazol 可抑制 Rieske Fe-S 中心的还原,防止过氧化氢的形成,通过分光光度法测定为 H2O2-过氧化物酶复合物。同样,线粒体细胞色素 c 的消耗也会抑制 H2O2 的形成,而添加细胞色素 c 可以恢复 H2O2 的形成。显然,阻止泛半醌形成的因素也会阻止 H2O2 的形成。他们还排除了泛醇作为 O2 的还原剂,在这些条件下泛醇仍然被还原。由于当粘噻唑添加到补充有琥珀酸盐和抗霉素 A 的线粒体中时,细胞色素 b 也保持完全还原,因此还原的细胞色素 b 也可能被排除为 O2 的还原剂。这些观察结果与 Q 循环反应一致,通过排除其他可能性,泛半醌成为复合物 III 中唯一能够将 O2 还原为 O2- 的还原电子载体。
Much evidence indicates that superoxide is generated from O2 in a cyanide-sensitive reaction involving a reduced component of complex III of the mitochondrial respiratory chain, particularly when antimycin A is present. Although it is generally believed that ubisemiquinone is the electron donor to O2, little experimental evidence supporting this view was reported. Experiments with succinate as electron donor in the presence of antimycin A in intact rat heart mitochondria, which contain much superoxide dismutase but little catalase, showed that myxothiazol, which inhibits reduction of the Rieske Fe-S center, prevented formation of hydrogen peroxide, determined spectrophotometrically as the H2O2-peroxidase complex. Similarly, depletion of the mitochondria of their cytochrome c also inhibited formation of H2O2, which was restored by addition of cytochrome c. Apparently, factors preventing the formation of ubisemiquinone also prevent H2O2 formation. They also exclude ubiquinol, which remains reduced under these conditions, as the reductant of O2. Since cytochrome b also remains fully reduced when myxothiazole is added to succinate- and antimycin A-supplemented mitochondria, reduced cytochrome b may also be excluded as the reductant of O2. These observations, which are consistent with the Q-cycle reactions, by exclusion of other possibilities leave ubisemiquinone as the only reduced electron carrier in complex III capable of reducing O2 to O2-.