Seattle Children's Research Institute, Seattle, WA, United States.
Mitochondrion. 2011 Jan;11(1):136-8. doi: 10.1016/j.mito.2010.09.002. Epub 2010 Sep 16.
Mitochondrial disorders are often associated with primary or secondary CoQ10 decrease. In clinical practice, Coenzyme Q10 (CoQ10) levels are measured to diagnose deficiencies and to direct and monitor supplemental therapy. CoQ10 is reduced by complex I or II and oxidized by complex III in the mitochondrial respiratory chain. Therefore, the ratio between the reduced (ubiquinol) and oxidized (ubiquinone) CoQ10 may provide clinically significant information in patients with mitochondrial electron transport chain (ETC) defects. Here, we exploit mutants of Caenorhabditis elegans (C. elegans) with defined defects of the ETC to demonstrate an altered redox ratio in Coenzyme Q9 (CoQ9), the native quinone in these organisms. The percentage of reduced CoQ9 is decreased in complex I (gas-1) and complex II (mev-1) deficient animals, consistent with the diminished activity of these complexes that normally reduce CoQ9. As anticipated, reduced CoQ9 is increased in the complex III deficient mutant (isp-1), since the oxidase activity of the complex is severely defective. These data provide proof of principle of our hypothesis that an altered redox status of CoQ may be present in respiratory complex deficiencies. The assessment of CoQ10 redox status in patients with mitochondrial disorders may be a simple and useful tool to uncover and monitor specific respiratory complex defects.
线粒体疾病通常与原发性或继发性 CoQ10 减少有关。在临床实践中，测量辅酶 Q10 (CoQ10) 水平以诊断缺乏症，并指导和监测补充治疗。CoQ10 在线粒体呼吸链中被复合物 I 或 II 还原，被复合物 III 氧化。因此，还原型（泛醇）和氧化型（泛醌）CoQ10 的比值可能为线粒体电子传递链 (ETC) 缺陷患者提供具有临床意义的信息。在这里，我们利用具有明确 ETC 缺陷的秀丽隐杆线虫 (C. elegans) 的突变体来证明这些生物体中天然醌 CoQ9 的氧化还原比发生了改变。在复合物 I（gas-1）和复合物 II（mev-1）缺陷的动物中，还原型 CoQ9 的百分比降低，与这些复合物的正常还原 CoQ9 的活性降低一致。正如预期的那样，在复合物 III 缺陷突变体（isp-1）中，还原型 CoQ9 增加，因为复合物的氧化酶活性严重缺陷。这些数据为我们的假设提供了原理证明，即呼吸复合物缺乏症可能存在 CoQ 的氧化还原状态改变。评估线粒体疾病患者的 CoQ10 氧化还原状态可能是发现和监测特定呼吸复合物缺陷的简单而有用的工具。
