MITOCHONDRIAL DYNAMICS--MORPHOLOGY/DIVISION/SEGREGATION

线粒体是在几乎所有真核生物中都存在的动态细胞器 细胞的位置、数量和结构都有显著的变化 在不同的细胞类型。 线粒体异常也与 与各种人类疾病有关。 事实上，我们对 介导线粒体动力学的分子机制。 在酵母 酿酒酵母，线粒体通常是细长的细胞器 在细胞周围形成网状结构。 酵母戏剧性地 调节其线粒体的形状，大小和数量， 细胞的生理状态。 我们提出了四种方法来识别 并分析介导线粒体形态的分子， 线粒体数量和线粒体位置。 MMM 1蛋白在介导线粒体形状中的功能是什么 和线粒体分离？ mmm 1突变体对温度敏感， 线粒体的外形。 在限制温度下， 细长的线粒体似乎迅速塌陷成大的球形， 细胞器 Mmm 1蛋白位于线粒体外膜， 膜，具有面向胞质溶胶的大羧基末端结构域。 MMM1 是一个新的基因，我们的研究结果提高了Mmm 1蛋白质 维持线粒体在一个延长的构象，通过介导的 细胞器与细胞骨架或其他外部物质的结合 框架. mmm 1突变体对生存力是温度敏感的， 致命性似乎是由于无法分离异常的- 使线粒体形成子细胞。 因此，线粒体的形状是 线粒体正常分离到子细胞所必需的 在细胞分裂期间。 为了确定Mmm 1 p的作用，我们建议：（1） 使用延时摄影检查Mmm 1 p功能缺陷的单个酵母细胞 荧光成像，（2）确定Mmm 1 p在 线粒体外膜，（3）询问Mmm 1 p是否位于 位点，（4）确定Mmm 1 p是否是多亚基复合物的一部分，以及（5） 询问线粒体与细胞骨架元素的结合，如 肌动蛋白或微管蛋白在mmm 1突变体中被破坏。 什么是BOM 1 P的作用，一个潜在的MMM 1 P相互作用蛋白质？ Bom 1 p被确定为一种分子遗传筛选蛋白质， 可能与Mmm 1 p相互作用。 我们已经证明Bom 1蛋白是 酵母细胞活力所必需的，Bom 1 p位于 线粒体内膜 此外，当Bom 1 p从 酵母细胞，细长的线粒体崩溃成球形细胞器 类似于在mmm 1突变体中看到的那些。 我们建议（1）隔离 温度敏感的Bom 1突变体，以确定Bom 1的作用 蛋白，和（2）测试Bom 1 p是否直接与Mmm 1 p相互作用， 酵母细胞. 酵母FTSZ同源物在线粒体中的作用 组织？ 我们最近在酵母线粒体中发现了 ftsZ是E. coli细胞分裂。 由于线粒体 被认为是由细菌产生的，我们将测试酵母是否 ftsZ相关蛋白在线粒体分裂中起作用。 线粒体凋亡缺陷的其他酵母突变体的特征。 除了mmm 1，我们还发现了23个在正常细胞中有缺陷的突变体。 线粒体形态、线粒体数量和线粒体 分布 我们建议进一步分析这些突变体， 它们在线粒体动力学中的作用

Mitochondria are dynamic organelles found in virtually all eukaryotic cells and show striking variations in their location, number and structure in different cell types. Mitochondrial abnormalities are also associated with a variety of human diseases. Virtually nothing is known about the molecular mechanisms that mediate mitochondrial dynamics. In the yeast Saccharomyces cerevisiae, mitochondria are usually elongated organelles which form a reticulum around the cell periphery. Yeast dramatically regulates the shape, size and number of its mitochondria according to the physiological state of the cell. We propose four approaches to identify and analyze the molecules that mediate mitochondrial morphology, mitochondrial number and mitochondrial location. WHAT IS THE FUNCTION OF THE MMM1 PROTEIN IN MEDIATING MITOCHONDRIAL SHAPE AND MITOCHONDRIAL SEGREGATION? mmm1 mutants are temperature-sensitive for the external shape of their mitochondria. At the restrictive temperature, elongated mitochondria appear to quickly collapse into large, spherical organelles. The Mmm1 protein is located in the mitochondrial outer membrane, with a large carboxyl-terminal domain facing the cytosol. MMM1 is a new gene and our results raise the possibility that the Mmm1 protein maintains mitochondria in an elongated conformation by mediating the binding of the organelle to the cytoskeleton or some other external framework. mmm1 mutants are temperature-sensitive for viability, and the lethality appears to result from the inability to segregate the aberrant- shaped mitochondria into daughter cells. Hence mitochondrial shape is essential for the normal segregation of mitochondria to daughter cells during cell division. To determine the role of Mmm1p, we propose to: (1) examine single yeast cells defective in Mmm1p function using time-lapse fluorescence imaging, (2) determine the topology of Mmm1p in the mitochondrial outer membrane, (3) ask if Mmm1p is located in contact sites, (4) determine if Mmm1p is part of a multisubunit complex, and (5) ask whether the binding of mitochondria to cytoskeletal elements, such as actin, or tubulin, are disrupted in mmm1 mutants. WHAT IS THE ROLE OF THE BOM1P, A POTENTIAL MMM1P-INTERACTING PROTEIN? Bom1p was identified as a molecular genetic screen for proteins that potentially interact with Mmm1p. We have shown that the Bom1 protein is essential for yeast cell viability, and that Bom1p is located in the mitochondrial inner membrane. Furthermore, when Bom1p is depleted from yeast cells, elongated mitochondria collapse into sphere-shaped organelles similar to those seen in mmm1 mutants. We propose to (1) isolate temperature-sensitive bom1 mutants to determine the role of the Bom1 protein, and (2) test whether Bom1p directly interacts with Mmm1p in the yeast cell. WHAT ROLE DOES A YEAST HOMOLOGUE OF BACTERIAL FTSZ PLAY IN MITOCHONDRIAL DIVISION? We have recently identified in yeast mitochondria a cognate of ftsZ, a protein required for E. coli cell division. Since mitochondria are thought to have arisen from bacteria, we will test whether the yeast ftsZ-related protein plays a role in mitochondrial division. CHARACTERIZE ADDITIONAL YEAST MUTANTS DEFECTIVE IN MITOCHONDRIAL DYNAMICS. In addition to mmm1, we identified 23 mutants defective in normal mitochondrial morphology, mitochondrial number, and mitochondrial distribution. We propose to further analyze these mutants to determine their role in mitochondrial dynamics.