Investigating the molecular mechanism of mitochondrial tethering

研究线粒体束缚的分子机制

• 批准号: 10113361
• 负责人: Laura L Lackner
• 金额: $ 29.42万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10113361
• 关键词: Address; Apoptotic; Architecture; Avidity; Binding; Biochemical; Biological; Biological Assay; Biology; Calcium; Cardiolipins; Cell Cycle Progression; Cell Death; Cell membrane; Cell physiology; Cells; Coiled-Coil Domain; Complex; Core Protein; Data; Defect; Disease; Exhibits; Goals; Grant; Homeostasis; Immune response; Lipid Binding; Lipids; Mediating; Membrane; Mitochondria; Mitochondrial Inheritance; Modeling; Molecular; Mothers; N-terminal; Neurons; Organelles; Outer Mitochondrial Membrane; PH Domain; Pattern; Phospholipids; Phosphorylation; Play; Positioning Attribute; Production; Protein Import; Proteins; Publishing; Regulation; Resolution; Role; SERPINA4 gene; Shapes; Site; Specificity; Structure; System; Techniques; Testing; Time; Work; Yeasts; cell motility; daughter cell; fitness; insight; interdisciplinary approach; interest; live cell imaging; mitochondrial membrane; protein complex; small molecule; spatiotemporal

Project Summary We are interested in the dynamic interplay between the intracellular distribution of mitochondria and cellular function. Mitochondria are important not only for cellular energy production but also play critical roles in cell cycle progression, differentiation, immune responses, lipid and calcium homeostasis, and apoptotic cell death. These diverse roles are intimately connected to mitochondrial shape and cellular position. Thus, it is not surprising aberrant mitochondrial architecture has been implicated in an ever-increasing number of diseases. Mitochondrial shape and position depend on the integrated and regulated activities of mitochondrial dynamics, motility, and tethering. A key question is how these activities are coordinated to drive the context-specific changes in the shape and position of mitochondria required to meet cellular needs. To begin to address this question, an understanding of the molecular basis of these mitochondrial activities is essential. While mitochondrial tethering plays a critical role in mitochondrial position and function in cells from yeast to neurons, it is the least understood of the activities that shape and position mitochondria. In the aims of this grant, we will address this deficit by exploiting the strengths of the facile yeast system and our expertise in cell biological and biochemical approaches to elucidate the molecular basis, mechanism, and regulation of two tether complexes that function in the distribution and inheritance of mitochondria. Understanding fundamental mechanisms used by cells to position mitochondria will provide insight into how regulated mitochondrial tethering can be harnessed to influence mitochondrial function and overall cellular homeostasis and fitness.

项目摘要 我们对线粒体细胞内分布之间的动态相互作用感兴趣 和细胞功能。线粒体不仅对细胞能量产生很重要，而且很重要 在细胞周期进展，分化，免疫反应，脂质和钙中起关键作用 稳态和凋亡细胞死亡。这些不同的角色与 线粒体形状和细胞位置。因此，不足为奇的异常线粒体 建筑与不断增加的疾病有关。线粒体形状 位置取决于线粒体动力学的综合和调节活动， 运动和束缚。一个关键问题是如何协调这些活动以推动 符合细胞所需的线粒体形状和位置的上下文特异性变化 需要。为了开始解决这个问题，对这些问题的理解 线粒体活动至关重要。线粒体绑扎在 线粒体位置和功能在从酵母到神经元的细胞中，最了解的 形状和位置线粒体的活动。以这笔赠款的目的，我们将解决这个问题 通过利用易感酵母系统的优势和我们在细胞生物学方面的专业知识来赤字 和生化方法，以阐明两个分子基础，机制和调节 系绳复合物在线粒体的分布和遗传中起作用。理解 细胞用于定位线粒体的基本机制将提供有关如何 可以利用受调节的线粒体绑扎来影响线粒体功能和 总体细胞稳态和健身。