The role of Por1 and its partner protein Om14 in mitochondrial protein import

Por1 及其伴侣蛋白 Om14 在线粒体蛋白输入中的作用

• 批准号: 528247081
• 负责人: Professor Dr. Thomas Becker
• 金额: --
• 依托单位: Institut für Biochemie und Molekularbiologie (IBMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/528247081?language=en
• 关键词: role; Por1; its; partner; protein

Mitochondrial biogenesis and functions depend on the import of more than 1000 proteins that are produced as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the entry site for almost all mitochondrial proteins. Subsequently, dedicated protein translocases sort the precursor proteins into the outer and inner membranes, the intermembrane space and matrix. While transport steps are understood to some detail only little is known how protein transport is modulated during metabolic adaptation. Mitochondrial protein biogenesis has to be adjusted to ensure the dramatic changes of the protein content during shift from fermentative to respiratory growth conditions, including strongly increased levels of proteins involved in respiratory metabolism. Recently, we have uncovered in baker`s yeast that the major outer membrane channel for metabolites and ions Por1 (also termed VDAC for voltage dependent anion channel) acts as coupling factor to promote import of carrier proteins. We furthermore found that Por1 interacts the protein translocases of the outer membrane, including the TOM complex, the sorting and assembly machinery (SAM complex) that inserts -barrel proteins and the mitochondria import (MIM complex) machinery that inserts proteins with -helical membrane anchor. Similarly, Om14 that forms a complex with Por1 interacts with TOM and MIM complexes, but not with the SAM complex. In this project, we will analyze the role of Por1 and Om14 in mitochondrial protein import and study their impact on outer membrane protein biogenesis. Our studies will reveal whether molecular coupling of mitochondrial protein translocases to Por1 and Om14 represents a new principle to modulate protein import capacity in response to metabolic adaptation during nutrient change. We will define the role of Por1 and Om14 to maintain mitochondrial protein content during metabolic adaptation. Since Om14 was reported to act as docking site for cytosolic ribosomes, we will investigate whether Om14 promotes co-translational protein import. Our studies will address the fundamental cell biological question how the mitochondrial protein biogenesis is adjusted in response to nutrient changes.

线粒体的生物发生和功能依赖于1000多种蛋白质的进口，这些蛋白质是作为胞质核糖体的前体产生的。外膜转位酶(TOM复合体)形成了几乎所有线粒体蛋白的进入部位。随后，专用蛋白转位酶将前体蛋白分选到外膜和内膜、膜间隙和基质中。虽然对转运步骤有一定的了解，但人们对代谢适应过程中蛋白质转运是如何调节的知之甚少。线粒体蛋白质的生物发生必须进行调整，以确保蛋白质含量在从发酵到呼吸生长条件的转变过程中发生戏剧性的变化，包括参与呼吸代谢的蛋白质水平的大幅增加。最近，我们在面包酵母中发现，代谢产物和离子的主要外膜通道Por1(又称电压依赖性阴离子通道VDAC)作为偶联因子促进载体蛋白的输入。我们进一步发现，Por1与外膜的蛋白质转位酶相互作用，包括TOM复合体、插入桶状蛋白质的分选和组装机械(SAM复合体)和插入带有螺旋膜锚定的蛋白质的线粒体输入(MIM复合体)机械。同样，与Por1形成复合体的Om14与Tom和MIM复合体相互作用，但不与SAM复合体相互作用。在本项目中，我们将分析Por1和Om14在线粒体蛋白输入中的作用，并研究它们对外膜蛋白生物发生的影响。我们的研究将揭示线粒体蛋白转位酶与Por1和Om14的分子偶联是否代表了在营养变化过程中调节蛋白质输入能力以响应代谢适应的新原理。我们将确定Por1和Om14在代谢适应过程中维持线粒体蛋白质含量的作用。由于Om14被报道为胞质核糖体的对接位点，我们将研究Om14是否促进共翻译蛋白输入。我们的研究将解决基本的细胞生物学问题，即线粒体蛋白的生物发生如何根据营养变化进行调整。