Mitochondrial dynamics and assembly in yeast

描述(由申请人提供)：这项研究计划的长期目标是了解一个重要的真核细胞器-线粒体的组装和动力学。线粒体的组装依赖于从胞浆中输入蛋白质，这一过程利用了线粒体内膜和外膜的复杂机制。尽管大部分进口设备已经确定，但还有其他进口部件有待确定。此外，关于前蛋白通过线粒体膜转运或插入脂双层疏水环境的机制，仍有许多悬而未决的问题。 线粒体也是动态细胞器，在精细控制下通过各种过程在细胞内不断融合、分裂和移动。线粒体在不同的细胞类型中也表现出各种各样的形状和数量。虽然线粒体的动态性质已经被记录了很多年，但对于调节细胞器的融合、分裂、分离和形状的分子或机制知之甚少。 为了进一步了解线粒体的组装和动力学，我们在酵母中分离出了线粒体功能缺陷的突变株酿酒酵母。我们建议继续对我们的遗传研究确定的线粒体蛋白质进行分析，并将重点关注以下问题： 1)线粒体的形状是如何建立的，线粒体DNA是如何维持的？ 2)线粒体蛋白输入的机制是什么？它与线粒体形态有何关系？ 3)线粒体分裂的机制是什么？ 4)线粒体融合的机制是什么？

DESCRIPTION (provided by applicant): The long-range goal of this research proposal is to understand the assembly and dynamics of an essential eukarydtic organelle, the mitochondrion. The assembly of mitochondria is dependent upon the import of proteins from the cytosol, a process that utilizes complicated machinery in both the mitochondrial inner and outer membranes. Although much of the import apparatus has been identified, additional import components await identification. In addition, many unanswered question remain about the mechanism by which preproteins are translocated across the mitochondrial membranes, or inserted into the hydrophobic environment of the lipid bilayer. Mitochondria are also dynamic organelles, continuously fusing, dividing and moving within cells by processes under exquisite control. Mitochondria also show a wide variety of shapes and numbers in different cell types. Although the dynamic nature of mitochondria has been documented for over TOO years, little is known about the molecules or mechanisms mediating the fusion, division, segregation and shape of the organelle. To further our understanding of mitochondrial assembly and dynamics, we have isolated mutants in the yeast, Saccharomyces cerevisiae, that are defective in mitochondrial function. We propose to continue our analyses of mitochondrial proteins identified by our genetic stusies, and will focus on the following questions: 1) How is mitochondrial shape established and mtDNA maintained? 2) What is the mechanism of mitochondrial protein import, and how is it related tomitochondrial shape? 3) What is the mechanism of mitochondrial division? 4) What is the mechanism of mitochondrial fusion?