Du Jianhai, Rountree Austin, Cleghorn Whitney M, Contreras Laura, Lindsay Ken J, Sadilek Martin, Gu Haiwei, Djukovic Danijel, Raftery Dan, Satrústegui Jorgina, Kanow Mark, Chan Lawrence, Tsang Stephen H, Sweet Ian R, Hurley James B
From the Department of Biochemistry, Department of Ophthalmology, University of Washington, Seattle, Washington 98109.
Diabetes and Obesity Center of Excellence.
J Biol Chem. 2016 Feb 26;291(9):4698-710. doi: 10.1074/jbc.M115.698985. Epub 2015 Dec 16.
Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternatively, production can be set by a signal that anticipates demand. In this report we investigate the hypothesis that signaling through phototransduction controls production of energy in mouse retinas. We found that respiration in mouse retinas is not coupled tightly to ATP consumption. By analyzing metabolic flux in mouse retinas, we also found that phototransduction slows metabolic flux through glycolysis and through intermediates of the citric acid cycle. We also evaluated the relative contributions of regulation of the activities of α-ketoglutarate dehydrogenase and the aspartate-glutamate carrier 1. In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines.
细胞内的能量产生必须与需求保持同步。光感受器在黑暗中利用ATP维持离子梯度,而在光照下则利用ATP支持光转导。使产生与消耗相匹配可以通过将产生直接与消耗相耦合来实现。或者,产生可以由预测需求的信号来设定。在本报告中,我们研究了通过光转导进行信号传导控制小鼠视网膜能量产生的假说。我们发现小鼠视网膜中的呼吸作用与ATP消耗并未紧密耦合。通过分析小鼠视网膜中的代谢通量,我们还发现光转导减缓了通过糖酵解和柠檬酸循环中间体的代谢通量。我们还评估了α-酮戊二酸脱氢酶和天冬氨酸-谷氨酸载体1活性调节的相对贡献。此外,对视网膜代谢组的全面分析表明,光转导还影响5'-GMP、5-磷酸核糖、酮体和嘌呤的稳态浓度。