Human NADH: ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?
Human NADH: ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?
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DOI：
10.1152/ajpcell.00194.2006
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发表时间：
2007-07-01
影响因子：
5.5
通讯作者：
Willems, Peter H. G. M.
中科院分区：
文献类型：
--
作者：
Koopman, Werner J. H.;Verkaart, Sjoerd;Willems, Peter H. G. M.
NADH功能障碍：泛醌氧化还原酶或复合物I（Cl），线粒体氧化磷酸化系统的第一个和最大的复合物，已经与多种人类疾病有关。为了证明CI量和活性与线粒体形状和细胞活性氧（ROS）水平之间的定量关系，我们最近结合了天然电泳和共聚焦和视频显微镜的皮肤成纤维细胞的健康对照组和儿童孤立CI缺乏症。个体线粒体在患者成纤维细胞中出现片段化和/或较少分支，CI量和活性严重降低（I类），而这些后者参数仅中度降低的患者细胞显示正常线粒体形态（II类）。此外，与II类细胞相比，I类细胞的细胞ROS水平显著增加。我们提出了一种机制，其中突变诱导的细胞量和CI活性的降低导致ROS水平的提高，这反过来又会诱导线粒体片段化，当细胞的抗氧化防御系统不适当平衡时。
Malfunction of NADH: ubiquinone oxidoreductase or complex I (CI), the first and largest complex of the mitochondrial oxidative phosphorylation system, has been implicated in a wide variety of human disorders. To demonstrate a quantitative relationship between CI amount and activity and mitochondrial shape and cellular reactive oxygen species (ROS) levels, we recently combined native electrophoresis and confocal and video microscopy of dermal fibroblasts of healthy control subjects and children with isolated CI deficiency. Individual mitochondria appeared fragmented and/or less branched in patient fibroblasts with a severely reduced CI amount and activity (class I), whereas patient cells in which these latter parameters were only moderately reduced displayed a normal mitochondrial morphology (class II). Moreover, cellular ROS levels were significantly more increased in class I compared with class II cells. We propose a mechanism in which a mutation-induced decrease in the cellular amount and activity of CI leads to enhanced ROS levels, which, in turn, induce mitochondrial fragmentation when not appropriately counterbalanced by the cell's antioxidant defense systems.