Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina

• Published in: The Journal of biological chemistry 2016-02, Vol.291 (9), p.4698-4710
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Amino Acid Transport Systems, Acidic - metabolism; anaerobic metabolism; Animals; Antiporters - metabolism; calcium; Calcium Signaling - radiation effects; Citric Acid Cycle - radiation effects; Cyclic GMP - metabolism; Electron Transport - radiation effects; Energy Metabolism - radiation effects; Eye Proteins - genetics; Eye Proteins - metabolism; Glycolysis - radiation effects; GTP-Binding Protein alpha Subunits - genetics; GTP-Binding Protein alpha Subunits - metabolism; Heterotrimeric GTP-Binding Proteins - genetics; Heterotrimeric GTP-Binding Proteins - metabolism; Ketoglutarate Dehydrogenase Complex - metabolism; Light; Light Signal Transduction; Metabolism; Metabolome - radiation effects; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; mitochondria; Oxygen Consumption - radiation effects; photoreceptor; phototransduction; retina; Retina - enzymology; Retina - metabolism; Retina - radiation effects; Tissue Culture Techniques; Transducin - genetics; Transducin - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.698985

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.