Molecular function of Mdm38 in protein export and biogenesis of respiratory chain complexes of the inner mitochondrial membrane

Mdm38 在蛋白质输出和线粒体内膜呼吸链复合物生物合成中的分子功能

• 批准号: 37395318
• 负责人: Professor Dr. Peter Rehling
• 金额: --
• 依托单位: Institut für Zellbiochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/37395318?language=en
• 关键词: Molecular; function; Mdm38; protein; export

Mdm38 is the S. cerevisiae homolog of the human Letm1, a protein that has been implicated in the pathogenesis of the Wolf-Hirschhorn Syndrome. We have found that Mdm38 is required for the biogenesis of respiratory chain complexes. The inner membrane protein Mdm38 interacts with mitochondrial ribosomes and participates in protein export across the inner mitochondrial membrane. Since the role of Mdm38 in these processes is unknown, we will analyze the molecular function of Mdm38 in protein transport and complex assembly in this project. Therefore, we will address the function of Mdm38 in the process of respiratory chain complex assembly with an in organello approach based on import and export analyses in mutant mitochondria. A central question is the molecular function of the Mdm38-ribosome association. Therefore, we will dissect the molecular interactions of Mdm38 with mitochondrial ribosomes and analyze other Mdm38 interacting proteins, which are part of the Mdm38 complex. It will be of particular interest to determine if Letm1 fulfills similar functions in human cells as Mdm38 in yeast. Therefore we will use an RNAi based approach to reduce levels of Letm1 in human cells and analyze mitochondrial functions such as morphology and respiratory chain complexes in these cells. Our analysis should allow novel insights into the function of Mdm38, the biogenesis of respiratory chain complexes and the molecular basis of a human disease.

Mdm38是人类Letm1的酿酒酵母同源物，Letm1是一种与沃尔夫-先天性巨结肠综合征的发病机制有关的蛋白质。我们发现MDM38是呼吸链复合体生物发生所必需的。内膜蛋白MDM38与线粒体核糖体相互作用，参与跨线粒体内膜的蛋白质输出。由于MDM38在这些过程中的作用尚不清楚，本项目将分析MDM38在蛋白质运输和复杂组装中的分子功能。因此，我们将基于突变线粒体的输入和输出分析，用细胞器内的方法来研究MDM38在呼吸链复合体组装过程中的作用。一个中心问题是MDM38-核糖体结合的分子功能。因此，我们将剖析mdm38与线粒体核糖体的分子相互作用，并分析属于mdm38复合体的其他mdm38相互作用蛋白。确定Letm1在人类细胞中是否与酵母中的mdm38具有类似的功能将是特别有意义的。因此，我们将使用基于RNAi的方法来降低人类细胞中Letm1的水平，并分析这些细胞中的线粒体功能，如形态和呼吸链复合体。我们的分析应该允许对MDM38的功能、呼吸链复合体的生物发生以及人类疾病的分子基础有新的见解。