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

线粒体的生物发生和功能依赖于1000多种蛋白质的输入，这些蛋白质作为细胞溶质核糖体上的前体产生。外膜转位酶（TOM复合物）形成几乎所有线粒体蛋白的进入位点。随后，专用的蛋白质移位酶将前体蛋白质分类到外膜和内膜、膜间空间和基质中。虽然运输步骤被理解到一些细节，但很少有人知道蛋白质运输在代谢适应过程中是如何调节的。必须调整线粒体蛋白质生物发生，以确保在从发酵到呼吸生长条件的转变期间蛋白质含量的急剧变化，包括呼吸代谢中涉及的蛋白质水平的强烈增加。最近，我们发现在面包酵母中，代谢物和离子Por 1的主要外膜通道（也称为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。我们还发现Por 1与外膜的蛋白质移位酶相互作用，包括TOM复合物、插入-桶蛋白的分选和组装机械（SAM复合物）和插入具有-螺旋膜锚的蛋白质的线粒体输入（MIM复合物）机械。 类似地，与Por 1形成复合物的Om 14与TOM和MIM复合物相互作用，但不与SAM复合物相互作用。在这个项目中，我们将分析Por 1和Om 14在线粒体蛋白输入中的作用，并研究它们对外膜蛋白生物合成的影响。我们的研究将揭示线粒体蛋白质移位酶与Por 1和Om 14的分子偶联是否代表了一种新的原理，可以调节蛋白质输入能力，以响应营养变化期间的代谢适应。我们将定义Por 1和Om 14在代谢适应过程中维持线粒体蛋白质含量的作用。由于Om 14被报道作为细胞溶质核糖体的对接位点，我们将研究Om 14是否促进共翻译蛋白的输入。我们的研究将解决基本的细胞生物学问题，即线粒体蛋白质的生物合成是如何响应营养变化而进行调整的。

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.