Lazarou Michael, Thorburn David R, Ryan Michael T, McKenzie Matthew
Department of Biochemistry, La Trobe University, 3086 Melbourne, Australia.
Biochim Biophys Acta. 2009 Jan;1793(1):78-88. doi: 10.1016/j.bbamcr.2008.04.015. Epub 2008 May 4.
Isolated complex I deficiency is the most common cause of respiratory chain dysfunction. Defects in human complex I result in energy generation disorders and they are also implicated in neurodegenerative disease and altered apoptotic signaling. Complex I dysfunction often occurs as a result of its impaired assembly. The assembly process of complex I is poorly understood, complicated by the fact that in mammals, it is composed of 45 different subunits and is regulated by both nuclear and mitochondrial genomes. However, in recent years we have gained new insights into complex I biogenesis and a number of assembly factors involved in this process have also been identified. In most cases, these factors have been discovered through their gene mutations that lead to specific complex I defects and result in mitochondrial disease. Here we review how complex I is assembled and the factors required to mediate this process.
孤立性复合物I缺乏是呼吸链功能障碍最常见的原因。人类复合物I的缺陷会导致能量生成紊乱，还与神经退行性疾病和凋亡信号改变有关。复合物I功能障碍常因组装受损而发生。复合物I的组装过程尚不清楚，在哺乳动物中，它由45个不同的亚基组成，并受核基因组和线粒体基因组调控，这使得情况更为复杂。然而，近年来我们对复合物I的生物合成有了新的认识，并且也鉴定出了许多参与这一过程的组装因子。在大多数情况下，这些因子是通过其基因突变被发现的，这些突变导致特定的复合物I缺陷并引发线粒体疾病。在此，我们综述复合物I是如何组装的以及介导这一过程所需的因子。
