Role of the Dynamin-Related GTPase, Mgm1p, in Mitochondrial Morphology

动力相关 GTP 酶 Mgm1p 在线粒体形态学中的作用

• 批准号: 0110899
• 负责人: Jodi Nunnari
• 金额: $ 20万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-10-01 至 2003-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0110899&HistoricalAwards=false
• 关键词: Role; Dynamin; Related; GTPase; Mgm1p

Mitochondria are semiautonomous intracellular organelles evolutionarily derived from endosymbiont prokaryotes. They are the primary site in eukaryotic cells where the energy of chemical bonds is oxidatively converted to a metabolically useful form. Mitochondria are therefore often referred to as the "powerhouses" of the eukaryotic cell. Like chloroplasts, mitochondria are separated from the cytoplasm of the cell by a double membrane system. The long term goal of this research project is to understand in molecular detail how the structure of the double-membraned mitochondrion is controlled. This is a complex problem because the chemical and physical structures of the outer membrane and inner membrane are different. In contrast to the outer membrane, the mitochondrial inner membrane is typically convoluted. These convolutions, referred to as cristae, form as a consequence of the greater surface area of the inner membrane, and presumably function to increase the organelle's ability to make energy. Interestingly, despite their distinct structures, current data suggest that fission and fusion of both membranes occur in tandem and that the molecular components that regulate these events are exclusively associated with the outer membrane. However, the range of cristae morphologies observed in cells suggests that the inner membrane is dynamic and that dedicated mechanisms and components exist to maintain its unique structure and perhaps to coordinate the behaviors of the two membranes. Virtually nothing is known about the mechanisms that regulate inner membrane structure in mitochondria. In addition to the outer membrane-associated dynamin-related GTPase, Dnm1p, analyses from Dr. Nunnari's laboratory indicate that a second dynamin-related GTPase, Mgm1p, is localized to the mitochondrial inner membrane and that inner membrane structure in mgm1 mutant cells is specifically aberrant. Members of the dynamin GTPase family share the common function to regulate the structure of various biological membranes. Thus, based on these findings, Dr. Nunnari hypothesizes that Mgm1p regulates the structure of mitochondria in cells by functioning to remodel the inner membranes. The experiments that will be done with support from this award will test this hypothesis utilizing a combination of genetic, biochemical, and cytological techniques.

线粒体是从内共生原核生物进化而来的半自主细胞内细胞器。 它们是真核细胞中化学键能量被氧化转化为代谢有用形式的主要部位。 因此，线粒体通常被称为真核细胞的“发电站”。 与叶绿体一样，线粒体通过双层膜系统与细胞的细胞质分开。该研究项目的长期目标是从分子角度详细了解双膜线粒体的结构是如何控制的。这是一个复杂的问题，因为外膜和内膜的化学和物理结构不同。与外膜相反，线粒体内膜通常是卷曲的。这些卷曲被称为嵴，是由于内膜表面积更大而形成的，并且可能起到增加细胞器产生能量的能力的作用。有趣的是，尽管它们的结构不同，但目前的数据表明，两种膜的裂变和融合是串联发生的，并且调节这些事件的分子成分仅与外膜相关。然而，在细胞中观察到的嵴形态范围表明内膜是动态的，并且存在专用机制和组件来维持其独特的结构，并可能协调两个膜的行为。事实上，人们对线粒体内膜结构的调节机制一无所知。 除了外膜相关的动力相关 GTP 酶 Dnm1p 之外，Nunnari 博士实验室的分析表明，第二种动力相关的 GTP 酶 Mgm1p 定位于线粒体内膜，并且 mgm1 突变细胞的内膜结构特别异常。动力 GTP 酶家族的成员具有调节各种生物膜结构的共同功能。因此，基于这些发现，Nunnari 博士推测 Mgm1p 通过重塑内膜来调节细胞中线粒体的结构。在该奖项的支持下进行的实验将结合遗传、生化和细胞学技术来检验这一假设。