Mechanisms linking mitochondrial form and function

连接线粒体形式和功能的机制

• 批准号: 10389944
• 负责人: Jodi M. Nunnari
• 金额: $ 12.6万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10389944
• 关键词: Address; Behavior; Businesses; Cell Death; Cell physiology; Cells; Complex; Crista ampullaris; DNA biosynthesis; DNA copy number; Data; Diabetes Mellitus; Disease; Ensure; Enzymes; Eukaryotic Cell; Event; Genome; Giant Cells; Health; Hereditary Disease; Homeostasis; Hot Spot; Human; Human body; Individual; Inner mitochondrial membrane; Laboratories; Link; Malignant Neoplasms; Mediating; Membrane; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Mitochondria; Mitochondrial DNA; Modeling; Natural Immunity; Nerve Degeneration; Neurodegenerative Disorders; Obesity; Organelles; Oxidative Phosphorylation; Pathogenesis; Pathway interactions; Positioning Attribute; Regulation; Research; Role; Signal Pathway; Site; System; Ubiquinone; Work; cell behavior; cell motility; insight; mitochondrial dysfunction; recruit; scaffold; transmission process

Summary Mitochondria are endosymbiotic organelles and have retained a reduced genome packaged into 100-1000 copies of nucleoids per cell, distributed within dynamic mitochondria “syncytia”. Mitochondria are the metabolic hubs of eukaryotic cells, producing ATP via oxidative phosphorylation and other critical building blocks. They have evolved to behave dynamically and to be an integrating platform for the assembly and regulation of signaling pathways, such as cell death and innate immunity. Given their central roles, it is not surprising that that mitochondrial dysfunction is associated with an increasingly large proportion of human inherited disorders and with common diseases, such as neurodegenerative disorders, metabolic syndromes, and cancer. To gain insight into the roles of mitochondria in sickness and in health, we are focused on how mitochondrial behavior is controlled within cells and how this behavior is intertwined with metabolism and cell behavior. Our current research addresses the outstanding questions of how mitochondrial DNA copy number and transmission is controlled in cells, how the mitochondrial inner membrane is differentiated into distinct domains and how mitochondrial behavior, metabolism and cell behavior are integrated. Addressing these questions will illuminate how mitochondria contribute to cellular homeostasis and pathogenesis.

概括 线粒体是内体细胞器，保留了降低的基因组 将每个细胞包装成100-1000份的核苷，分布在动态内 线粒体“合成”。线粒体是真核细胞的代谢中心，产生 ATP通过氧化磷酸化和其他关键的构建块。他们已经发展到 动态行为，成为组装和调节的集成平台 信号通路，例如细胞死亡和先天免疫。鉴于它们的核心角色，这是 毫不奇怪，线粒体功能障碍与越来越大的 人类遗传疾病和常见疾病的比例，例如 神经退行性疾病，代谢综合征和癌症。洞悉 线粒体在疾病和健康中的作用，我们专注于线粒体 行为在细胞内受到控制，以及这种行为如何与代谢交织在一起 细胞行为。我们目前的研究解决了如何 线粒体DNA拷贝数和传输在细胞中控制，如何 线粒体内膜分化为不同的结构域以及线粒体如何 行为，新陈代谢和细胞行为被整合。解决这些问题将 阐明线粒体如何有助于细胞稳态和发病机理。