Admin Supp: Investigating the molecular mechanism of mitochondrial tethering

管理补充：研究线粒体束缚的分子机制

• 批准号: 10796458
• 负责人: Laura L Lackner
• 金额: $ 5.14万
• 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 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10796458
• 关键词: Address; Apoptotic; Architecture; Calcium; Cell Cycle Progression; Cell Death; Cell physiology; Cells; Communication; Disease; Dissection; Goals; Grant; Health; Homeostasis; Immune response; Lipids; Microscope; Mitochondria; Modeling; Molecular; Neurons; Organelles; Physiological; Play; Positioning Attribute; Production; Regulation; Role; Shapes; Site; Structure; System; Techniques; Work; Yeasts; cell motility; experimental study; fitness; human disease; insight; interest; men who have sex with men; mitochondrial membrane; novel therapeutic intervention

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. It is well appreciated that mitochondrial division, fusion, and motility all contribute to the overall distribution of mitochondria within a cell. However, the critical contributions of actively tethering the organelle to specific cellular sites and structures, including other organelles, are becoming increasingly evident. While tethering plays a critical role in mitochondrial positioning, interorganelle contact, and, consequently, cellular function in cells from yeast to neurons, the molecular mechanisms and regulation are poorly understood. In the aims of this grant, we will address this deficit by using a mitochondria-ER-cortex tether in yeast as a model to understand the mechanism and regulation of mitochondrial tethers and the multifunctional mitochondrial membrane contact sites they create. The proposed work will address the exciting and unexpected impacts mitochondrial tethers have on cellular organization and function. The goals are to uncover fundamental mechanisms used by mitochondrial tethers to position mitochondria and form interorganelle contacts and elucidate the functional and physiological consequences of these activities. In doing so, this work will provide insight into novel therapeutic strategies for a range of human disease conditions in which the manipulation of the position and the contacts made by mitochondria can be used to positively influence cellular health and homeostasis. The requested supplement is for the purchase of an MSM 400 Dissecting Microscope. The system is critical to support experiments that directly impact and address the goals put forth for this project. By acquiring the MSM 400 Dissecting Microscope, an essential but soon to be non-functional tetrad dissection microscope will be replaced and new techniques directly relevant to the project will be feasible.

项目摘要 我们对线粒体和细胞的细胞内分布之间的动态相互作用感兴趣 功能。线粒体不仅对细胞能量产生很重要，而且在细胞周期中起关键作用 进展，分化，免疫反应，脂质和钙稳态以及凋亡细胞死亡。这些 各种作用与线粒体形状和细胞位置密切相关。因此，毫不奇怪 线粒体建筑的异常涉及到不断增加的疾病。很好 感谢线粒体分裂，融合和运动性都有助于线粒体的整体分布 在单元格内。但是，主动将细胞器绑定到特定细胞部位的关键贡献和 包括其他细胞器在内的结构变得越来越明显。绑扎在 线粒体定位，企业间接触，因此，从酵母到细胞中的细胞功能 神经元，分子机制和调节知之甚少。为了这笔赠款的目的，我们将 通过在酵母中使用线粒体 - 皮质系绳作为了解机制的模型来解决这种赤字 以及线粒体系的调节及其创建的多功能线粒体膜接触位点。 拟议的工作将解决线粒体系数对细胞的激动人心和意外的影响 组织和功能。目标是发现线粒体系数使用的基本机制 位置线粒体并形成跨加工触点并阐明功能和生理 这些活动的后果。这样，这项工作将为您提供新的治疗策略的见解 一系列人类疾病状况，在其中操纵位置和接触 线粒体可用于积极影响细胞健康和稳态。请求的补充是 用于购买MSM 400解剖显微镜。该系统对于支持直接的实验至关重要 影响并解决该项目的目标。通过获取MSM 400解剖显微镜， 必不可少的，但很快将是非功能性四元解剖显微镜，并直接取代新技术 与该项目相关的是可行的。