Koopman Werner J H, Verkaart Sjoerd, Visch Henk Jan, van Emst-de Vries Sjenet, Nijtmans Leo G J, Smeitink Jan A M, Willems Peter H G M
Department of Membrane Biochemistry, Radboud University Nijmegen Medical Centre, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Am J Physiol Cell Physiol. 2007 Jul;293(1):C22-9. doi: 10.1152/ajpcell.00194.2006. Epub 2007 Apr 11.
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.
泛醌氧化还原酶即复合体I（CI），是线粒体氧化磷酸化系统的首个也是最大的复合体，其功能异常与多种人类疾病有关。为了证明CI含量与活性、线粒体形态及细胞活性氧（ROS）水平之间的定量关系，我们最近将天然电泳与健康对照受试者及孤立性CI缺乏症儿童的皮肤成纤维细胞的共聚焦和视频显微镜检查相结合。在CI含量和活性严重降低的患者成纤维细胞中（I类），单个线粒体呈现碎片化和/或分支减少，而CI含量和活性仅中度降低的患者细胞则显示出线粒体形态正常（II类）。此外，与II类细胞相比，I类细胞中的细胞ROS水平显著升高。我们提出了一种机制，即突变导致的CI细胞含量和活性降低会导致ROS水平升高，进而在未被细胞抗氧化防御系统适当抵消时诱导线粒体碎片化。
