Protein integration into the mitochondrial outer membrane

蛋白质整合到线粒体外膜

• 批准号: 140350888
• 负责人: Professor Dr. Doron Rapaport
• 金额: --
• 依托单位: Interfakultäres Institut für Biochemie (IFIB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/140350888?language=en
• 关键词: Protein; integration; into; mitochondrial; outer

Most mitochondrial proteins are encoded by nuclear DNA, synthesized in the cytosol, and imported into the various mitochondrial sub-compartments. Proteins of the outer membrane contain non-cleavable targeting and sorting signals. Currently, these signals and the mechanism of protein integration into the mitochondrial outer membrane are unclear. One goal of the proposed study is to investigate the membrane integration pathway of proteins that span the outer membrane once. To that end, we will combine an insertion assay based on site-specific modification with the usage of lipid vesicles and mitochondria isolated from various strains. Pull-down assays will be used to identify a putative insertase for such proteins. Furthermore, the molecular mechanism by which precursors of ß-barrel proteins are targeted to mitochondria and sorted within the organelle will be studied. To address this questions we will search for targeting signals in these proteins and will analyze the relay of precursor proteins from the TOM to the TOB complex. Furthermore, we will use a genetic screen to study the function of single components of the TOB machinery. These experiments will provide new insights into the biogenesis of mitochondrial outer membrane proteins.

大多数线粒体蛋白质由核DNA编码，在细胞质中合成，并输入到各种线粒体亚区室中。外膜的蛋白质含有不可切割的靶向和分选信号。目前，这些信号和蛋白质整合到线粒体外膜的机制尚不清楚。这项研究的一个目标是研究跨外膜一次的蛋白质的膜整合途径。为此，我们将结合联合收割机的插入试验的基础上，位点特异性修饰的脂质囊泡和线粒体分离自各种菌株的使用。下拉测定将用于鉴定此类蛋白质的推定插入酶。此外，将研究微管蛋白前体靶向线粒体并在细胞器内分选的分子机制。为了解决这个问题，我们将在这些蛋白质中寻找靶向信号，并分析前体蛋白从TOM到TOB复合物的中继。此外，我们将使用遗传筛选来研究TOB机制的单个组件的功能。这些实验将为线粒体外膜蛋白的生物发生提供新的见解。

项目成果

The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

• DOI: 10.1128/mcb.00227-13
• 发表时间: 2013-10-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Papic, Drazen;Elbaz-Alon, Yael;Rapaport, Doron
• 通讯作者: Rapaport, Doron

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

• DOI: 10.1128/mcb.00107-15
• 发表时间: 2015-09-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Sauerwald, Julia;Jores, Tobias;Rapaport, Doron
• 通讯作者: Rapaport, Doron