MITOCHONDRIAL DYNAMICS-MORPHOLOGY/DIVISION/SEGREGATION

线粒体是几乎所有真核细胞中都存在的重要细胞器，在许多不同的细胞类型中，线粒体在数量、位置和形状上表现出惊人的异质性。由于介导这些过程的分子和机制在很大程度上是未知的，我们已经分离并分析了酵母中线粒体融合和分裂缺陷、线粒体分离到子细胞以及线粒体形状维持缺陷的突变体。我们的研究已经确定了几种介导线粒体形态发生不同方面的蛋白质。我们对这些新蛋白质提出了以下问题。Fzo1p、Ugo1p和Ugo2p在线粒体融合中的作用是什么？Fzo1突变体线粒体融合有缺陷，含有大量线粒体片段。Fzo1p是一种外膜定位的GTPase。Ugo1p和Ugo2p是在线粒体融合突变基因筛选中发现的新蛋白。Dnm1p和Net2p如何介导线粒体分裂？Dnm1和net2突变体线粒体分裂有缺陷，在这些细胞中，线粒体形成一个由相互连接的小管网络组成的单一细胞器。Dnm1p是一种与动力蛋白相关的gtp酶，位于线粒体分裂位点的线粒体表面。Net2p是一种新的dnm1p相互作用蛋白，也位于线粒体表面。Mmm1p和Slm1p在线粒体形状和分离中的作用是什么？mm1突变体在线粒体的形状、线粒体与子细胞的分离以及线粒体DNA （mtDNA）的维持方面存在缺陷。我们发现Mmm1蛋白位于线粒体外膜上，呈离散的点状结构，也与mtDNA类核共定位。我们推测Mmm1p是线粒体内外膜蛋白质复合物的一部分，该复合物在细胞质溶胶中的肌动蛋白细胞骨架和基质中的mtDNA之间形成连接。Slm1是在筛选与mmm1突变相互作用的突变中鉴定出来的。与Mmm1p一样，Slm1p位于线粒体外膜，是线粒体形状所必需的。线粒体动力学还需要哪些蛋白质？最近，收集了大约6000株酵母菌株，每个株在不同的ORF中被破坏。使用基于显微镜的分析，我们将筛选线粒体形状，分离，分裂或融合缺陷的突变体。

Mitochondria are essential organelles found in virtually all eukaryotic cells and show a striking heterogeneity in their number, location and shape in many different cell types. Since the molecules and mechanisms that mediate these processes are largely unknown, we have isolated and analyzed mutants in the yeast Saccharomyces cervisiae defective in mitochondrial fusion and division, in the segregation of mitochondria to daughter cells, and in the maintenance of mitochondrial shape. Our studies have identified several proteins that mediate different aspects of mitochondrial morphogenesis. We are asking the following questions about these new proteins. What is the function of Fzo1p, Ugo1p, and Ugo2p in mitochondrial fusion? fzo1 mutants are defective in mitochondrial fusion and contain numerous mitochondrial fragments. Fzo1p is an outer membrane-localized GTPase. Ugo1p and Ugo2p are new proteins identified in a genetic screen for mitochondrial fusion mutants. How do Dnm1p and Net2p mediate mitochondrial division? dnm1 and net2 mutants are defective in mitochondrial division, and in these cells mitochondria form a single organelle consisting of a network of interconnected tubules. Dnm1p is a dynamin-related GTP-ase located on the mitochondrial surface at sites of mitochondrial division. Net2p is a novel Dnm1p-interacting protein also located on the mitochondrial surface. What is the role of Mmm1p and Slm1p in mitochondrial shape and segregation? mmm1 mutants are defective in the shape of their mitochondria, in the segregation o the mitochondria to daughter cells, and in the maintenance of mitochondrial DNA (mtDNA). We find the Mmm1 protein located in the mitochondrial outer membrane in discrete, punctate structures that also colocalize with mtDNA nucleoids. We speculate that Mmm1p is part of a complex of proteins in the mitochondrial outer and inner membrane that forms a connection between the actin cytoskeleton in the cytosol, and mtDNA in the matrix. slm1 was identified in a screen for mutations that interact with mmm1 mutants. Slm1p, like Mmm1p, is located in the mitochondrial outer membrane and is required for mitochondrial shape. What other proteins are required for mitochondrial dynamics? Recently, a collection of approximately 6000 yeast strains, each disrupted in a different ORF, has been generated. Using a microscope-based assay, we will screen this collection for mutants defective in mitochondria shape, segregation, division or fusion.