Photoreceptor Mitochondria and Ca2+ Dynamics

光感受器，启动视觉的神经元，必须适应以在敌对的环境中生存 蜂窝环境。在视网膜中，它们暴露在破坏性的光辐射中， 体验100倍波动的细胞内钙离子，位于血液附近 血管具有高水平的氧气，并且比大多数其他类型的细胞更快地利用ATP 在身体里。为了确保最佳的功能和生存，光感受器必须有 用于维护健康线粒体的强大系统。这将涉及到受监管的 线粒体清除、生物发生、融合和分裂之间的平衡。这里 我们建议对它们的昼夜节律进行全面的分析。 过程及其与线粒体结构和代谢变化的关系 功能。我们利用了老鼠和斑马鱼模型的优点，并 我们研究新陈代谢和光感受器生物学的专业知识。在目标1中，我们将 确定光感受器线粒体功能的日常和昼夜变化 结构。在目标2中，我们评估了线粒体清除和生物发生以及在 目的3我们研究线粒体流动性背后的细胞触发因素。总而言之， 我们正在问几个问题，这些问题都是为了理解 线粒体动态平衡。我们将检查线粒体的生物发生，清除， 不同时间形态、数量、影响运动和代谢的因素 无论在白天还是在黑暗中。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健康和 功能。

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.