Molecular Bioenergetics Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Cluster of Excellence Frankfurt Macromolecular Complexes, Goethe-University, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Germany.
OXPHOS Biogenesis Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Cell Metab. 2017 Jan 10;25(1):128-139. doi: 10.1016/j.cmet.2016.09.002. Epub 2016 Oct 6.
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.
线粒体复合物 I 是呼吸链中最大的整合膜酶，由线粒体和核基因组编码的 44 个不同亚基组成。其生物合成是一个高度复杂和多方面的过程，至少涉及 14 个额外的组装因子。这些亚基如何组装成一个功能性的复合物 I，以及组装因子在何处发挥作用，在很大程度上是未知的。在这里，我们应用动态复合物组学分析方法来阐明人线粒体复合物 I 的组装及其进一步整合到呼吸链超复合物中。我们描述了除一个亚基以外的所有亚基逐步整合到一系列不同的组装中间产物中，并与已知和假定的组装因子相关联，这些因子以前并未涉及到这个过程。由此产生的复合物 I 组装的详细而全面的模型与最近的结构数据以及这个多蛋白复合物的显著模块化结构完全一致。
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