Fontanesi Flavia, Soto Ileana C, Horn Darryl, Barrientos Antoni
Departments of Neurology, The John T. Macdonald Foundation Center for Medical Genetics, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Am J Physiol Cell Physiol. 2006 Dec;291(6):C1129-47. doi: 10.1152/ajpcell.00233.2006. Epub 2006 Jun 7.
Cytochrome c-oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in the regulation of aerobic production of energy. Biogenesis of eukaryotic COX involves the coordinated action of two genomes. Three mitochondrial DNA-encoded subunits form the catalytic core of the enzyme, which contains metal prosthetic groups. Another 10 subunits encoded in the nuclear DNA act as a protective shield surrounding the core. COX biogenesis requires the assistance of >20 additional nuclear-encoded factors acting at all levels of the process. Expression of the mitochondrial-encoded subunits, expression and import of the nuclear-encoded subunits, insertion of the structural subunits into the mitochondrial inner membrane, addition of prosthetic groups, assembly of the holoenzyme, further maturation to form a dimer, and additional assembly into supercomplexes are all tightly regulated processes in a nuclear-mitochondrial-coordinated fashion. Such regulation ensures the building of a highly efficient machine able to catalyze the safe transfer of electrons from cytochrome c to molecular oxygen and ultimately facilitate the aerobic production of ATP. In this review, we will focus on describing and analyzing the present knowledge about the different regulatory checkpoints in COX assembly and the dynamic relationships between the different factors involved in the process. We have used information mostly obtained from the suitable yeast model, but also from bacterial and animal systems, by means of large-scale genetic, molecular biology, and physiological approaches and by integrating information concerning individual elements into a cellular system network.
细胞色素c氧化酶（COX）是线粒体呼吸链的末端酶，在有氧能量产生的调节中起关键作用。真核生物COX的生物合成涉及两个基因组的协同作用。三个线粒体DNA编码的亚基形成该酶的催化核心，其中含有金属辅基。另外10个由核DNA编码的亚基作为围绕核心的保护屏障。COX生物合成需要20多种额外的核编码因子在该过程的各个层面发挥作用。线粒体编码亚基的表达、核编码亚基的表达和导入、结构亚基插入线粒体内膜、辅基的添加、全酶的组装、进一步成熟形成二聚体以及进一步组装成超复合物，都是以核-线粒体协调的方式严格调控的过程。这种调控确保构建一个高效的机器，能够催化电子从细胞色素c安全转移到分子氧，并最终促进ATP的有氧产生。在这篇综述中，我们将重点描述和分析目前关于COX组装中不同调控检查点以及该过程中涉及的不同因素之间动态关系的知识。我们主要利用了从合适的酵母模型以及细菌和动物系统中获得的信息，通过大规模遗传、分子生物学和生理学方法，并将关于各个元件的信息整合到细胞系统网络中。
