Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, U.K.
Department of Pathophysiology, Sechenov First Moscow State Medical University, 119048 Moscow, Russia.
Biochem Soc Trans. 2019 Dec 20;47(6):1963-1969. doi: 10.1042/BST20191042.
Mitochondria control vitally important functions in cells, including energy production, cell signalling and regulation of cell death. Considering this, any alteration in mitochondrial metabolism would lead to cellular dysfunction and the development of a disease. A large proportion of disorders associated with mitochondria are induced by mutations or chemical inhibition of the mitochondrial complex I - the entry point to the electron transport chain. Subunits of the enzyme NADH: ubiquinone oxidoreductase, are encoded by both nuclear and mitochondrial DNA and mutations in these genes lead to cardio and muscular pathologies and diseases of the central nervous system. Despite such a clear involvement of complex I deficiency in numerous disorders, the molecular and cellular mechanisms leading to the development of pathology are not very clear. In this review, we summarise how lack of activity of complex I could differentially change mitochondrial and cellular functions and how these changes could lead to a pathology, following discrete routes.
线粒体控制着细胞中至关重要的功能，包括能量产生、细胞信号转导和细胞死亡的调节。考虑到这一点，线粒体代谢的任何改变都会导致细胞功能障碍和疾病的发展。很大一部分与线粒体相关的疾病是由线粒体复合物 I 的突变或化学抑制引起的，复合物 I 是电子传递链的入口点。酶 NADH：泛醌氧化还原酶的亚基由核 DNA 和线粒体 DNA 编码，这些基因的突变会导致心脏和肌肉病理学以及中枢神经系统疾病。尽管复合物 I 缺乏与许多疾病明显相关，但导致病理学发展的分子和细胞机制尚不清楚。在这篇综述中，我们总结了缺乏活性的复合物 I 如何通过不同的途径改变线粒体和细胞功能，以及这些变化如何导致病理学。
