Complexome Profiling Identifies TMEM126B as a Component of the Mitochondrial Complex I Assembly Complex
Complexome Profiling Identifies TMEM126B as a Component of the Mitochondrial Complex I Assembly Complex
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DOI：
10.1016/j.cmet.2012.08.009
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发表时间：
2012-10-01
期刊：
影响因子：
29
通讯作者：
Brandt, Ulrich
中科院分区：
文献类型：
--
作者：
Heide, Heinrich;Bleier, Lea;Brandt, Ulrich
大分子复合物是许多生物过程中必不可少的参与者。它们通常是巨大的、动态的、相当不稳定的；研究它们的方法很少。我们用blue-native和大孔blue-native凝胶电泳分离了大鼠心脏线粒体的天然复合物组，并对其成分进行了质谱分析。迁移模式的相似性允许分层聚类成相互作用概况，代表了对整个细胞器的可溶性和膜结合复合物的全面分析。这种自下而上的方法的力量被充分表征的线粒体多蛋白复合物验证。发现TMEM126B与已知的线粒体复合体I的组装因子CIA30、Ecsit和Acad9同源。我们建议将这个复杂的线粒体命名！复合物I组装（MCIA）复合物。此外，我们证明了TMEM126B是复合体i的组装所必需的。总之，复合体分析是一种强大而公正的技术，可以识别以前被忽视的大型多蛋白复合体的成分。
Macromolecular complexes are essential players in numerous biological processes. They are often large, dynamic, and rather labile; approaches to study them are scarce. Covering masses up to similar to 30 MDa, we separated the native complexome of rat heart mitochondria by blue-native and large-pore blue-native gel electrophoresis to analyze its constituents by mass spectrometry. Similarities in migration patterns allowed hierarchical clustering into interaction profiles representing a comprehensive analysis of soluble and membrane-bound complexes of an entire organelle. The power of this bottom-up approach was validated with well-characterized mitochondrial multiprotein complexes. TMEM126B was found to comigrate with known assembly factors of mitochondrial complex I, namely CIA30, Ecsit, and Acad9. We propose terming this complex mitochondria! complex I assembly (MCIA) complex. Furthermore, we demonstrate that TMEM126B is required for assembly of complex I. In summary, complexome profiling is a powerful and unbiased technique allowing the identification of previously overlooked components of large multiprotein complexes.