Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells
Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells
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DOI：
10.1016/j.mito.2006.07.008
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发表时间：
2006-10-01
期刊：
影响因子：
4.4
通讯作者：
Boldogh, Istvan
中科院分区：
文献类型：
--
作者：
Bacsi, Attila;Woodberry, Mitchell;Boldogh, Istvan
3-硝基丙酸 (3-NPA) 是线粒体电子传递链复合体 II 上琥珀酸脱氢酶 (SDH) 的抑制剂，可诱导细胞能量缺乏和氧化应激相关的神经毒性。在本研究中，我们确定了线粒体中活性氧产生的位点。 3-NPA 增加了在复合物 I 底物丙酮酸 + 苹果酸上呼吸的线粒体中 O-2(.-) 的产生，这种作用被鱼藤酮完全抑制。在复合物 I 和/或 II 底物存在的情况下，抗霉素 A 会增加 O-2(.-) 的产生。添加3-NPA显着增加了抗霉素A诱导的与复合物I底物一起孵育的线粒体产生的O-2(.-)，但3-NPA抑制了由复合物II底物琥珀酸驱动的O-2(.-)形成。 0.6 μM 时，myxothiazol 可抑制复合物 III，但仅部分降低复合物 I 活性，并允许 3-NPA 诱导 O-2(.-) 形成；然而，在 40 μM 的 myxothiazol（完全抑制复合物 I 和 III）下，通过复合物 I 底物消除了线粒体呼吸中 O-2(.-) 的产生。这些结果表明，在存在 3-NPA 的情况下，线粒体从呼吸复合物 II 中泛醇库和 3-NPA 块之间的位点生成 O-2(.-)。 (c) 2006 年 Elsevier B.V. 和线粒体研究协会。版权所有。
3-Nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase (SDH) at complex II of the mitochondrial electron transport chain induces cellular energy deficit and oxidative stress-related neurotoxicity. In the present study, we identified the site of reactive oxygen species production in mitochondria. 3-NPA increased O-2(.-) generation in mitochondria respiring on the complex I substrates pyruvate + malate, an effect fully inhibited by rotenone. Antimycin A increased O-2(.-) production in the presence of complex I and/or II substrates. Addition of 3-NPA markedly increased antimycin A-induced O-2(.-) production by mitochondria incubated with complex I substrates, but 3-NPA inhibited O-2(.-) formation driven with the complex II substrate succinate. At 0.6 mu M, myxothiazol inhibits complex III, but only partially decreases complex I activity, and allowed 3-NPA-induced O-2(.-) formation; however, at 40 mu M myxothiazol (which completely inhibits both complexes I and III) eliminated O-2(.-) production from mitochondria respiring via complex I substrates. These results indicate that in the presence of 3-NPA, mitochondria generate O-2(.-) from a site between the ubiquinol pool and the 3-NPA block in the respiratory complex II. (c) 2006 Elsevier B.V. and Mitochondria Research Society. All rights reserved.