Control of Photoreceptor Metabolism

描述(申请人提供)：光感受器是代谢最活跃的细胞之一。它们有非常大的线粒体，并以非常快的速度消耗氧气。糖酵解和氧化磷酸化产生的能量必须与这些高度专业化的神经元的能量消耗保持同步。感光器在黑暗中比在光线中消耗氧气的速度略快，但消耗能量的过程在本质上是非常不同的。在特定条件下造成能量生产和消耗失衡的突变可能会带来压力，导致氧化损伤和细胞死亡。这项提议的目的是建立一个量化模型，以了解光感受器能量的产生和消耗。具体目标1是开发方法来量化各种生化反应消耗光感受器中高能代谢物的速率。在特定目标2中，我们将使用这些方法，结合小鼠的特定基因突变，来研究光感受器产生和消耗能量的过程。在目标2中，我们还将确定如何监管能源生产。具体目标3侧重于钙结合蛋白Recovery in在能量代谢中所起的作用。了解这些高代谢神经元是如何产生和消耗能量的，将为理解光感受器功能提供基础信息。这些研究还将为为什么特定类别的遗传突变会导致压力和视网膜疾病提供亟需的见解。

DESCRIPTION (provided by applicant): Photoreceptors are among the most metabolically active cells. They have extraordinarily large mitochondria and consume oxygen at exceptional rates. Energy production by glycolysis and oxidative phosphorylation must keep pace with energy consumption in these highly specialized neurons. Photoreceptors consume oxygen slightly faster in darkness than in light, but the processes that consume energy are qualitatively very different. Mutations that create an imbalance of energy production and consumption under specific conditions may introduce stresses that cause oxidative damage and cell death. The aim of this proposal is to establish a quantitative model to understand production and consumption of energy in photoreceptors. Specific aim 1 is to develop methods to quantify the rates at which various biochemical reactions consume high energy metabolites in photoreceptors. In specific Aim 2 we will use those methods, together with specific genetic mutations in mice, to investigate the processes in photoreceptors that produce and consume energy. In aim 2 we also will determine how energy production is regulated. Specific aim 3 focuses on the role that the calcium-binding protein, recoverin, plays in energy metabolism. Understanding how energy is produced and consumed in these highly metabolic neurons will provide information fundamental to understanding photoreceptor function. These studies also will provide much-needed insights into why specific classes of inherited mutations cause stress and retinal disease.