Modular assembly of yeast cytochrome oxidase.

Modular assembly of yeast cytochrome oxidase.
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DOI:
10.1091/mbc.e12-10-0749
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发表时间:
2013-02
影响因子:
3.3
通讯作者:
Tzagoloff A
Tzagoloff A
中科院分区:
生物学3区
文献类型:
--
作者:
McStay GP;Su CH;Tzagoloff A

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脉冲追踪标记分离的酵母线粒体确定新的组装中间体Cox 1 p,其组成的特点,并顺序排列。结果表明,细胞色素氧化酶组装从单独的模块,每个模块由不同的线粒体和核基因产物。酵母细胞色素氧化酶(考克斯)的生物发生的研究确定了Cox 1 p,三个核心亚基之一,在两个高分子量的复合物结合的监管/组装因子表达该亚基。在本研究中,我们使用脉冲追踪标记实验结合分离的线粒体,以确定新的Cox 1 p中间体,并将它们放置在一个有序的途径。我们的研究结果表明,在其同化成考克斯,Cox 1 p过渡通过5个中间体,区分其组成的辅助因子和两个进口的8个亚基。我们提出了一个模型的考克斯生物合成中,Cox 1 p和其他两个线粒体基因产物,Cox 2 p和Cox 3 p,构成独立的组装模块,每个都有自己的补充亚基。与它们的细菌对应物不同,它们只由单个核心亚基组成,线粒体模块结合形成全酶的最终序列可能在进化过程中是保守的。
Pulse-chase labeling of isolated yeast mitochondria identifies new assembly intermediates of Cox1p, characterizes their compositions, and orders them sequentially. The results indicate that cytochrome oxidase is assembled from separate modules, each consisting of different mitochondrial and nuclear gene products. 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.