BIOENERGETICS

生物能量学

• 批准号: 7183910
• 负责人: David Nicholls
• 金额: $ 19.97万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183910
• 关键词: Acute; Age; Aging; Alzheimer' s Disease; Animal Disease Models; Apoptotic; Benchmarking; Bioenergetics; Biological Assay; Brain; Cancer Model; Cell Line; Cell Nucleus; Cell Respiration; Cell membrane; Cells; Cerebral cortex; Chronic; Collaborations; Complement; Complex; Corpus striatum structure; Cytoplasmic matrix; Data; Disease; Disease model; Dopaminergic Cell; Electron Transport; Environment; Event; Fibroblasts; Glutathione; Hand; Human; In Vitro; Individual; Investigation; Knock-out; Link; Manganese Superoxide Dismutase; Measurement; Membrane Potentials; Mitochondria; Modeling; Modification; Mus; Nerve; Neurons; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; Pathway interactions; Phenotype; Proteomics; Protons; Purpose; Reactive Oxygen Species; Research Personnel; Resources; Respiration; Respiratory Chain; Role; Stimulus; Stress; Sulfhydryl Compounds; Superoxides; Synaptosomes; TP53 gene; Testing; Tissues; Titrations; age related; age related neurodegeneration; base; design; programs; research study; respiratory; size; tau Proteins

The three component Projects in this application are each devoted to one or more aspects of the functional bioenergetic consequences of changes in mitochondrial composition or environment in age-related animal disease models, whether in isolated nerve terminals (projects 1 and 3) cell lines (projects 1 and 2) or primary neuronal cultures (project 1). The broad objectiveof the Bioenergetics Core is to provide a common platform across each Project for the design, execution and analysis of die subset of experiments that involve an analysis of mitochondrial function. The projects are focused around mitochondrial respiratory chain complexes (project 1), the mutual interactions of the glutathione thiol redox control pathways and the mitochondrion (projects 1,2),the consequences of defective scavenging of superoxide generated by the respiratory chain (projects 2, 3) and the interactions of p53 with the mitochondrion (project 2). The specific aims of the Bioenergetics Coreare: 1. To provide an intellectual and practical resource to assist Project Leaders in the design and analysisof specific experiments whose purpose is to investigate mitochondrial bioenergetic function in the variety of age-related disease models studied in the program. 2. To provide detailed and comprehensive assistance to the projects in the planning, execution and interpretation of assays of mitochondrial function in a variety of models including cell lines, fibroblasts, primary neurons and isolated nerve terminals. Assays will include respiration of cells, synaptosomes and isolated mitochondria, proton leak quantification,respiratory capacity, ATP turnover, mitochondrial and plasma membrane potentials, mitochondrial and cytoplasmic reactive oxygen species, ATP/ ADP ratios, NAD(P)H and glutathione levels, redox status, and cytoplasmicand matrix free Ca2+. 3. To utilize isolated mitochondria from brain and other tissues as models to test and generate hypotheses concerning the quantitative consequences for the mitochondrial bioenergetic network of subtle modulations in respiratory capacity, membrane potential, proton leak, glutathione pool size, pro-apoptotic stimulietc. 4. To aid the integration of the results obtained in the bioenergetic studies from the three Projects along with structural data from Proteomics Core C into a coherent picture of mitochondrial stress, aging and age- related disease.

该应用程序中的三个组成项目分别致力于功能的一个或多个方面 年龄相关动物线粒体组成或环境变化的生物能后果 疾病模型，无论是在分离的神经末梢（项目 1 和 3）细胞系（项目 1 和 2）还是原代细胞中 神经元培养（项目 1）。 生物能量学核心的广泛目标是为每个项目提供一个通用平台 涉及线粒体分析的实验子集的设计、执行和分析 功能。这些项目重点围绕线粒体呼吸链复合物（项目 1）、 谷胱甘肽硫醇氧化还原控制途径和线粒体的相互作用（项目 1,2）， 呼吸链产生的超氧化物清除缺陷的后果（项目 2、3）和 p53 与线粒体的相互作用（项目 2）。 生物能量学核心的具体目标是： 1. 提供知识和实践资源，协助项目负责人设计和分析 特定实验，其目的是研究各种线粒体生物能功能 该项目研究了与年龄相关的疾病模型。 2. 为项目的策划、执行和实施提供详细、全面的协助 解释各种模型中线粒体功能的测定，包括细胞系、成纤维细胞、 初级神经元和孤立的神经末梢。检测包括细胞呼吸、突触体和 分离线粒体、质子泄漏定量、呼吸能力、ATP 周转、线粒体和 质膜电位、线粒体和细胞质活性氧、ATP/ADP 比率、 NAD(P)H 和谷胱甘肽水平、氧化还原状态以及细胞质和基质游离 Ca2+。 3. 利用从大脑和其他组织分离的线粒体作为模型来测试和产生假设 关于线粒体生物能量网络的微妙调节的定量后果 呼吸能力、膜电位、质子泄漏、谷胱甘肽池大小、促凋亡刺激等。 4. 帮助整合三个项目的生物能研究结果以及 将蛋白质组学核心 C 的结构数据转化为线粒体应激、衰老和年龄的连贯图景 相关疾病。