Control of Photoreceptor Metabolism

描述（由申请人提供）：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，以非常快的速度消耗氧气。在这些高度特化的神经元中，糖酵解和氧化磷酸化产生的能量必须与能量消耗保持同步。光感受器在黑暗中消耗氧气的速度比在光照下略快，但消耗能量的过程在性质上非常不同。在特定条件下造成能量产生和消耗不平衡的突变可能会引入导致氧化损伤和细胞死亡的压力。该建议的目的是建立一个定量模型来了解光感受器中能量的产生和消耗。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的高能代谢物的速率。在具体的目标2中，我们将使用这些方法，以及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，恢复，在能量代谢中发挥的作用。了解这些高度代谢的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型的遗传突变会导致压力和视网膜疾病提供急需的见解。

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.