Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Mol Biol Cell. 2013 Feb;24(4):440-52. doi: 10.1091/mbc.E12-10-0749. Epub 2012 Dec 24.
Previous studies of yeast cytochrome oxidase (COX) biogenesis identified Cox1p, one of the three mitochondrially encoded core subunits, in two high-molecular weight complexes combined with regulatory/assembly factors essential for expression of this subunit. In the present study we use pulse-chase labeling experiments in conjunction with isolated mitochondria to identify new Cox1p intermediates and place them in an ordered pathway. Our results indicate that before its assimilation into COX, Cox1p transitions through five intermediates that are differentiated by their compositions of accessory factors and of two of the eight imported subunits. We propose a model of COX biogenesis in which Cox1p and the two other mitochondrial gene products, Cox2p and Cox3p, constitute independent assembly modules, each with its own complement of subunits. Unlike their bacterial counterparts, which are composed only of the individual core subunits, the final sequence in which the mitochondrial modules associate to form the holoenzyme may have been conserved during evolution.
先前对酵母细胞色素氧化酶（COX）生物发生的研究鉴定出 Cox1p，它是三个线粒体编码的核心亚基之一，与调节/组装因子结合形成两种高分子量复合物，这些因子对于这个亚基的表达至关重要。在本研究中，我们使用脉冲追踪标记实验与分离的线粒体结合，以鉴定新的 Cox1p 中间体，并将其置于有序的途径中。我们的结果表明，在 Cox1p 被整合到 COX 之前，它要经历五个中间体，这些中间体的区别在于它们的辅助因子组成和八个导入的亚基中的两个。我们提出了 COX 生物发生的模型，其中 Cox1p 和另外两个线粒体基因产物 Cox2p 和 Cox3p 构成独立的组装模块，每个模块都有自己的亚基组成。与仅由单个核心亚基组成的细菌对应物不同，线粒体模块在形成全酶时的最终序列可能在进化过程中得到了保守。
