The Assembly Pathway of Mitochondrial Respiratory Chain Complex I
The Assembly Pathway of Mitochondrial Respiratory Chain Complex I
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DOI：
10.1016/j.cmet.2016.09.002
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发表时间：
2017-01-10
期刊：
影响因子：
29
通讯作者：
Nijtmans, Leo
中科院分区：
文献类型：
--
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
线粒体复合物I是呼吸链中最大的膜酶，由线粒体和核基因组中编码的44个不同亚基组成。它的生物合成是一个高度复杂和多方面的过程，涉及至少14个额外的组装因子。这些亚基如何组装成一个功能复合体I，以及组装因子在哪里发挥作用，在很大程度上是未知的。在这里，我们采用了动态复合体分析方法来阐明组装的人线粒体复合物I和它的进一步纳入呼吸链超复合物。我们描绘了逐步纳入所有，但一个亚基到一系列不同的组装中间体和他们的协会与已知的和推定的组装因子，这并没有牵连在这个过程中之前。由此产生的详细和全面的模型，复杂的我组装是完全符合最近的结构数据和显着的模块化架构，这种多蛋白质复合物。
Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes. We delineate the stepwise incorporation of all but one subunit into a series of distinct assembly intermediates and their association with known and putative assembly factors, which had not been implicated in this process before. The resulting detailed and comprehensive model of complex I assembly is fully consistent with recent structural data and the remarkable modular architecture of this multiprotein complex.