MECHANISMS OF MITOCHONDRIAL FISSION AND FUSION

线粒体裂变和融合机制

• 批准号: 6619130
• 负责人: Janet M. Shaw
• 金额: $ 6.76万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6619130
• 关键词: Saccharomyces cerevisiae; adenosine triphosphate; affinity chromatography; binding proteins; chemical binding; enzyme activity; fungal proteins; guanosinetriphosphatases; magnesium ion; membrane activity; mitochondria; protein protein interaction

DESCRIPTION (applicant's description): Changes in mitochondrial morphology and copy number are associated with a variety of human diseases including neurological disorders and some types of cancer. Although the metabolic functions of mitochondria have been extensively studied, the molecular mechanisms that regulate mitochondrial membrane dynamics are not understood. In the current funding period, we characterized two different GTPases in S. cerevisiae that regulate mitochondrial morphology and copy number. Dnm1p is a dynamin-related GTPase that acts on the outer mitochondrial membrane to regulate fission. Fzo1p (fuzzy onions) is a transmembrane GTPase that regulates mitochondrial docking and/or fusion. Both GTPases have human homologues that, when mutated, cause defects in mitochondrial morphology. These findings illustrate how effectively yeast can be used as a tool to study the molecular mechanisms that control mitochondrial dynamics in human cells. During the next funding period, we will continue to study mitochondrial fission and fusion in yeast using a combination of genetic, molecular and biochemical approaches. Specifically, we propose: 1) to identify and characterize SFZ genes/proteins required for mitochondrial fission, 2) to determine the role of Fzo1p self-interactions in mitochondrial fusion, 3) to screen for binding partners that interact with Fzo1p in its GTP-bound state, and 4) to develop an in vitro assay for mitochondrial fusion. The studies we propose will provide new information about the molecular and biochemical basis of mitochondrial fission and fusion in eukaryotic cells.

描述（申请人的描述）：线粒体形态的变化和 拷贝数与各种人类疾病有关 神经系统疾病和某些类型的癌症。虽然是代谢 线粒体的功能已被广泛研究，分子 不了解调节线粒体膜动力学的机制。在 当前的资金期，我们在S中表征了两个不同的GTPase。 调节线粒体形态和拷贝数的酿酒酵母。 DNM1P是a 作用于外部线粒体膜的动力蛋白相关的GTPase 调节裂变。 fzo1p（模糊洋葱）是一种调节的跨膜GTPase 线粒体对接和/或融合。两个GTPases都有人类的同源物， 突变时，导致线粒体形态的缺陷。这些发现 说明如何有效地将酵母用作研究分子的工具 控制人类细胞中线粒体动力学的机制。在下一个 资金期，我们将继续研究线粒体裂变和融合 酵母结合了遗传，分子和生化方法。 具体而言，我们建议：1）识别和表征SFZ基因/蛋白质 线粒体裂变所必需的，2）确定FZO1P的作用 线粒体融合中的自我交互，3）筛选绑定伙伴 该与FZO1P在其GTP结合状态下与FZO1P相互作用，4）开发体外 线粒体融合的测定。我们提出的研究将提供新的 有关线粒体裂变的分子和生化基础的信息 和真核细胞中的融合。