Perocchi Fabiana, Jensen Lars J, Gagneur Julien, Ahting Uwe, von Mering Christian, Bork Peer, Prokisch Holger, Steinmetz Lars M
European Molecular Biology Laboratory, Heidelberg, Germany.
PLoS Genet. 2006 Oct 20;2(10):e170. doi: 10.1371/journal.pgen.0020170.
Mitochondria carry out specialized functions; compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarked measures of protein interactions, a network of mitochondria was constructed in their cellular context, including extra-mitochondrial proteins. This network also integrates data from different organisms to expand the known mitochondrial biology beyond the information in the existing databases. Our network brings together annotated and predicted functions into a single framework. This enabled, for the entire system, a survey of mutant phenotypes, gene regulation, evolution, and disease susceptibility. Furthermore, we experimentally validated the localization of several candidate proteins and derived novel functional contexts for hundreds of uncharacterized proteins. Our network thus advances the understanding of the mitochondrial system in yeast and identifies properties of genes underlying human mitochondrial disorders.
线粒体执行特定功能；它们被分隔开，但又整合到细胞的代谢和信号传导过程中。尽管已经鉴定出许多线粒体蛋白，但了解它们之间的功能相互关系一直是一项挑战。在这里，我们构建了一个全面的线粒体系统网络。我们整合了全基因组数据集，以生成一份准确且全面的线粒体成分清单。结合经过基准测试的蛋白质相互作用测量方法，在细胞环境中构建了一个线粒体网络，包括线粒体外的蛋白质。该网络还整合了来自不同生物体的数据，以将已知的线粒体生物学扩展到现有数据库中的信息之外。我们的网络将注释和预测的功能整合到一个单一框架中。这使得能够对整个系统进行突变体表型、基因调控、进化和疾病易感性的调查。此外，我们通过实验验证了几种候选蛋白的定位，并为数百种未表征的蛋白推导了新的功能背景。因此，我们的网络推进了对酵母中线粒体系统的理解，并确定了人类线粒体疾病潜在基因的特性。
