Remacle Claire, Barbieri M Rosario, Cardol Pierre, Hamel Patrice P
Genetics of Microorganisms Laboratory, Department of Life Sciences, University of Liège, Liège, Belgium.
Mol Genet Genomics. 2008 Aug;280(2):93-110. doi: 10.1007/s00438-008-0350-5. Epub 2008 Jun 18.
With more than 40 subunits, one FMN co-factor and eight FeS clusters, complex I or NADH:ubiquinone oxidoreductase is the largest multimeric respiratory enzyme in the mitochondria. In this review, we focus on the diversity of eukaryotic complex I. We describe the additional activities that have been reported to be associated with mitochondrial complex I and discuss their physiological significance. The recent identification of complex I-like enzymes in the hydrogenosome, a mitochondria-derived organelle is also discussed here. Complex I assembly in the mitochondrial inner membrane is an intricate process that requires the cooperation of the nuclear and mitochondrial genomes. The most prevalent forms of mitochondrial dysfunction in humans are deficiencies in complex I and remarkably, the molecular basis for 60% of complex I-linked defects is currently unknown. This suggests that mutations in yet-to-be-discovered assembly genes should exist. We review the different experimental systems for the study of complex I assembly. To our knowledge, in none of them, large screenings of complex I mutants have been performed. We propose that the unicellular green alga Chlamydomonas reinhardtii is a promising system for such a study. Complex I mutants can be easily scored on a phenotypical basis and a large number of transformants generated by insertional mutagenesis can be screened, which opens the possibility to find new genes involved in the assembly of the enzyme. Moreover, mitochondrial transformation, a recent technological advance, is now available, allowing the manipulation of all five complex I mitochondrial genes in this organism.
复合体I或NADH：泛醌氧化还原酶含有40多个亚基、一个FMN辅因子和八个铁硫簇，是线粒体中最大的多聚体呼吸酶。在这篇综述中，我们聚焦于真核生物复合体I的多样性。我们描述了据报道与线粒体复合体I相关的其他活性，并讨论了它们的生理意义。这里还讨论了最近在氢化酶体（一种线粒体衍生的细胞器）中发现的类复合体I酶。线粒体内膜中的复合体I组装是一个复杂的过程，需要核基因组和线粒体基因组的协同作用。人类中最常见的线粒体功能障碍形式是复合体I缺陷，值得注意的是，目前60%的与复合体I相关缺陷的分子基础尚不清楚。这表明尚未发现的组装基因中应该存在突变。我们综述了用于研究复合体I组装的不同实验系统。据我们所知，在这些系统中都没有对复合体I突变体进行大规模筛选。我们提出单细胞绿藻莱茵衣藻是进行此类研究的一个有前景的系统。复合体I突变体可以很容易地在表型基础上进行评分，并且可以筛选通过插入诱变产生的大量转化体，这为找到参与该酶组装的新基因提供了可能性。此外，线粒体转化这项最近的技术进展现在已经可用，它允许对该生物体中所有五个复合体I线粒体基因进行操作。
