Molecular basis and cellular roles of mitochondria-ER contact sites

线粒体-ER接触位点的分子基础和细胞作用

• 批准号: 10189369
• 负责人: Jodi M. Nunnari
• 金额: $ 7.3万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189369
• 关键词: Address; Architecture; Area; Cell Death; Cells; Cellular biology; Communication; Endoplasmic Reticulum; Etiology; Eukaryotic Cell; Functional disorder; Grant; Homeostasis; Ions; Link; Mammalian Cell; Mitochondria; Mitochondrial DNA; Molecular; Natural Immunity; Organelles; Phospholipids; Physiology; Positioning Attribute; Production; Regulation; Respiration; Role; Signal Pathway; Site; Yeasts; cell motility; comparative; human disease; insight; new therapeutic target; parent grant; recruit; transmission process

Abstract of parent grant 5R37GM097432: Mitochondria perform fundamental functions in eukaryotic cells, including ATP production via respiration and cellular ion and phospholipid homeostasis. They also serve as platforms to integrate signaling pathways such as cell death and innate immunity. Mitochondrial functions are tightly linked to mitochondrial form, established through separate, but somehow coordinated machines that control dynamics, positioning, motility and mitochondrial DNA (mtDNA) transmission. The endoplasmic reticulum (ER) has emerged as an integral and pervasive player in the regulation of mitochondrial form and function. The ER exerts its role through contacts with mitochondria, which we hypothesize create specialized microdomains, which can recruit and/or modulate effectors that control and integrate mitochondrial physiology with other organelles and signaling pathways. In most cases, however, the molecular composition of ER-mitochondria contacts is poorly defined and their exact mechanisms of action, their functional scope and modes of communication are poorly understood. In the aims of this grant, we will address these deficits by exploring the molecular basis and functions of different types of ER- mitochondria contact sites in yeast and we will extend our findings to mammalian cells using comparative and forward strategies. New information in this area of cell biology will provide insight into the general architecture and roles of ER contacts and their regulation of mitochondrial function and cellular homeostasis to more accurately reveal role of mitochondria in human diseases that result from mitochondrial and ER dysfunction.

母基金5 R37 GM 097432摘要： 线粒体在真核细胞中执行基本功能，包括ATP的产生 通过呼吸和细胞离子和磷脂稳态。它们也是 整合信号通路的平台，如细胞死亡和先天免疫。 线粒体的功能与线粒体的形式紧密相连， 独立的，但不知何故协调的机器，控制动力，定位， 线粒体DNA（mtDNA）的传递。内质网（ER）具有 作为线粒体形式调节的一个整体和普遍的参与者出现， 功能ER通过与线粒体接触发挥作用，我们假设 创建专门的微区，可以招募和/或调节控制 并将线粒体生理学与其他细胞器和信号通路整合在一起。在 然而，大多数情况下，ER-线粒体接触的分子组成很差， 其确切的作用机制、功能范围和 沟通不太清楚。在这项赠款的目的，我们将解决这些问题， 通过探索不同类型的ER的分子基础和功能， 我们将把我们的发现扩展到哺乳动物细胞 采用比较和前瞻战略。细胞生物学领域的新信息将 深入了解ER接触的一般结构和作用及其对 线粒体功能和细胞内稳态，以更准确地揭示 线粒体和ER功能障碍导致的人类疾病中的线粒体。