MitoP2: An Integrative Tool for the Analysis of the Mitochondrial Proteome

MitoP2: An Integrative Tool for the Analysis of the Mitochondrial Proteome
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DOI:
10.1007/s12033-008-9100-5
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发表时间:
2008-11-01
影响因子:
2.6
通讯作者:
Prokisch, Holger
Prokisch, Holger
中科院分区:
医学4区
文献类型:
--
作者:
Elstner, Matthias;Andreoli, Christophe;Prokisch, Holger

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线粒体对于正常细胞代谢和维持至关重要。线粒体功能障碍与一系列人类疾病有关,从罕见的单基因疾病到常见的多因素疾病。对于理解细胞器功能重要的是其组分的分配,尽管预计超过1,500种蛋白质参与哺乳动物线粒体功能,但迄今为止只有约900种蛋白质被合理确定地分配给线粒体。目前正在通过单蛋白研究和高通量方法获得线粒体蛋白质组的完整清单。为了对科学界产生最大的价值,这些数据需要进行结构化、探索和定制。为此目的,建立并维持了MitoP2数据库(www.mitop2.de),以便纳入这些数据。中央数据库包含人工评估的酵母,小鼠和人类参考蛋白,这些蛋白显示了线粒体位置的令人信服的证据。此外,来自全基因组方法的建议蛋白质定位的条目被整合,并用于为每个候选人编制组合评分,这提供了线粒体定位的最佳估计。此外,它整合了物种之间的同源性信息,包括酿酒酵母,小鼠,人类,拟南芥和粗糙脉孢菌,从而相互增强跨物种的证据。与其他已知的数据库相比,MitoP2考虑到了蛋白质被估计为位于结肠的可靠性,如本文所述。多种搜索功能,以及致病基因和可用小鼠模型的信息,使MitoP2成为人类线粒体病理学遗传研究的宝贵工具。
Mitochondria are crucial for normal cell metabolism and maintenance. Mitochondrial dysfunction has been implicated in a spectrum of human diseases, ranging from rare monogenic to common multifactorial disorders. Important for the understanding of organelle function is the assignment of its constituents, and although over 1,500 proteins are predicted to be involved in mammalian mitochondrial function, so far only about 900 are assigned to mitochondria with reasonable certainty. Continuing efforts are being taken to obtain a complete inventory of the mitochondrial proteome by single protein studies and high-throughput approaches. To be of best value for the scientific community this data needs to be structured, explored, and customized. For this purpose, the MitoP2 database (http://www.mitop2.de) was established and is maintained in order to incorporate such data. The central database contains manually evaluated yeast, mouse, and human reference proteins, which show convincing evidence of a mitochondrial location. In addition, entries from genome-wide approaches that suggest protein localization are integrated and serve to compile a combined score for each candidate, which provides a best estimate of mitochondrial localization. Furthermore, it integrates information on the orthology between species, including Saccharomyces cerevisiae, mouse, human, Arabidopsis thaliana, and Neurospora crassa, thus mutually enhancing evidence across species. In contrast to other known databases, MitoP2 takes into account the reliability by which the protein is estimated as being mitochondrially located, as described herein. Multiple search functions, as well as information on disease causing genes and available mouse models, makes MitoP2 a valuable tool for the genetic investigation of human mitochondrial pathology.