Photoreceptor Mitochondria and Ca2+ Dynamics

光感受器线粒体和 Ca2 动力学

• 批准号: 9905173
• 负责人: Susan E Brockerhoff
• 金额: $ 39.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905173
• 关键词: Age related macular degeneration; Biogenesis; Biological Models; Biology; Blood Vessels; Circadian Rhythms; Cone; Disease; Ensure; Environment; Equilibrium; Exposure to; Functional disorder; Glycolysis; Health; Homeostasis; Light; Maintenance; Metabolic; Metabolism; Mitochondria; Modeling; Morphology; Movement; Mus; Neurons; Organelles; Pathogenesis; Photoreceptors; Process; Production; Radiation; Retina; Retinitis Pigmentosa; Stargardt' s disease; Stress; Structure; Synapses; System; Time; Vision; Work; Zebrafish; cell motility; cell type; circadian; circadian regulation; cone-rod dystrophy; experience; metabolic abnormality assessment; mitochondrial dysfunction; mouse model; photoreceptor degeneration; prevent

Photoreceptors, the neurons that initiate vision, must adapt to survive in a hostile cellular environment. In the retina they are exposed to damaging light radiation, experience 100-fold fluctuations in intracellular Ca2+, are located near blood vessels with high levels of O2, and use ATP faster than most other types of cells in the body. To ensure optimal function and survival, photoreceptors must have a robust system for maintaining healthy mitochondria. This would involve a regulated balance between mitochondrial clearance, biogenesis, fusion and fission. Here we propose a comprehensive analysis of the circadian regulation of these processes and how they relate to changes in mitochondrial structure and metabolic function. We exploit advantages of both the mouse and the zebrafish models and our expertise studying metabolism and photoreceptor biology. In Aim 1 we will define daily and circadian changes in photoreceptor mitochondria function and structure. In Aim 2 we evaluate mitochondrial clearance and biogenesis and in Aim 3 we examine cellular triggers underlying mitochondrial mobility. In summary, we are asking several questions that are all directed toward understanding mitochondria homeostasis. We will examine mitochondrial biogenesis, clearance, morphology, number, factors influencing motility and metabolism at different times of day both in light and dark. This will provide a broad and impactful overview of how these processes are coordinated to optimize photoreceptor health and function.

光感受器，即启动视觉的神经元，必须适应在敌对环境中生存 细胞环境。在视网膜中，它们暴露在破坏性的光辐射下， 细胞内 Ca2+ 经历 100 倍波动，位于血液附近 具有高水平 O2 的血管，并且比大多数其他类型的细胞更快地使用 ATP 在身体里。为了确保最佳功能和生存，光感受器必须具有 维持健康线粒体的强大系统。这将涉及一个受监管的 线粒体清除、生物发生、融合和裂变之间的平衡。这里 我们建议对这些生物的昼夜节律调节进行全面分析 过程以及它们与线粒体结构和代谢变化的关系 功能。我们利用小鼠和斑马鱼模型的优点 我们的专业知识是研究新陈代谢和光感受器生物学。在目标 1 中，我们将 定义光感受器线粒体功能的每日和昼夜变化，以及 结构。在目标 2 中，我们评估线粒体清除和生物发生，并在 目标 3 我们检查线粒体流动性的细胞触发因素。总之， 我们提出了几个旨在理解的问题 线粒体稳态。我们将检查线粒体的生物发生、清除、 不同时期的形态、数量、影响运动和代谢的因素 白天和黑夜。这将提供一个广泛而有影响力的概述 如何协调这些过程以优化感光器的健康以及 功能。