The Tim8-Tim13 complex of Neurospora crassa functions in the assembly of proteins into both mitochondrial membranes
The Tim8-Tim13 complex of Neurospora crassa functions in the assembly of proteins into both mitochondrial membranes
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DOI：
10.1074/jbc.m313037200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Nargang, FE
中科院分区：
文献类型：
--
作者：
Hoppins, SC;Nargang, FE
酵母中的TIM8和TIM13蛋白存在于线粒体膜间间隙，并形成异源寡聚复合体，参与TIM23转位酶的中心成分TIM23的输入。在这里，我们分离了粗枝脉孢菌的tim8和tim13突变体，并表明缺乏Tim8-Tim13复合体的线粒体缺乏外膜β桶蛋白Tom40和porin的输入。交联研究表明，Tom40前体与TIM8-TIM13复合体接触。该复合体在Tom40组装途径的早期就参与其中，因为只有在Tom40导入的初始阶段才能检测到交联链。在缺乏Tim8-Tim13复合体的线粒体中，Tom40前体出现在先前描述的Tom40组装的早期中间体中比在野生型线粒体中出现得慢。因此，我们的数据提出了一个模型，在该模型中，Tom40组装的第一步可能是与Tim8-Tim13复合体相互作用。和在酵母中一样，当膜电位降低时，粗毛杆菌TIM23前体被低效地输入到缺乏Tim8-Tim13复合体的线粒体中。TIM23的导入中间体也可以与该复合体交联，这表明Tim8-Tim13膜间空间复合体在线粒体外膜和内膜中发现的蛋白质的导入中具有双重作用。
The Tim8 and Tim13 proteins in yeast are known to exist in the mitochondrial intermembrane space and to form a hetero-oligomeric complex involved in the import of the mitochondrial inner membrane protein Tim23, the central component of the TIM23 translocase. Here, we have isolated tim8 and tim13 mutants in Neurospora crassa and have shown that mitochondria lacking the Tim8-Tim13 complex were deficient in the import of the outer membrane beta-barrel proteins Tom40 and porin. Cross-linking studies showed that the Tom40 precursor contacts the Tim8-Tim13 complex. The complex is involved at an early point in the Tom40 assembly pathway because cross-links can only be detected during the initial stages of Tom40 import. In mitochondria lacking the Tim8-Tim13 complex, the Tom40 precursor appears in a previously characterized early intermediate of Tom40 assembly more slowly than in wild type mitochondria. Thus, our data suggest a model in which one of the first steps in Tom40 assembly may be interaction with the Tim8-Tim13 complex. As in yeast, the N. crassa Tim23 precursor was imported inefficiently into mitochondria lacking the Tim8-Tim13 complex when the membrane potential was reduced. Tim23 import intermediates could also be cross-linked to the complex, suggesting a dual role for the Tim8-Tim13 intermembrane space complex in the import of proteins found in both the outer and inner mitochondrial membranes.