title: Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina.
abstract: 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.
authors.affiliation: From the Department of Biochemistry, Department of Ophthalmology, University of Washington, Seattle, Washington 98109.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Du
authors.affiliation: Diabetes and Obesity Center of Excellence.
authors.forename: Austin
authors.initials: A
authors.lastname: Rountree
authors.affiliation: From the Department of Biochemistry.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Cleghorn
authors.affiliation: Department of Molecular Biology, Centre for Molecular Biology Severo Ochoa, Universidad Autonoma de Madrid-Consejo Superior de Investigaciones Científicas, CIBER of Rare Diseases (CIBERER), and Health Research Institute Jimenez Diaz Foundation, Autonomous University of Madrid, 28049 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Contreras
authors.affiliation: From the Department of Biochemistry.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Lindsay
authors.affiliation: Department of Chemistry.
authors.forename: Martin
authors.initials: M
authors.lastname: Sadilek
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Gu
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine.
authors.forename: Danijel
authors.initials: D
authors.lastname: Djukovic
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine.
authors.forename: Dan
authors.initials: D
authors.lastname: Raftery
authors.affiliation: Department of Molecular Biology, Centre for Molecular Biology Severo Ochoa, Universidad Autonoma de Madrid-Consejo Superior de Investigaciones Científicas, CIBER of Rare Diseases (CIBERER), and Health Research Institute Jimenez Diaz Foundation, Autonomous University of Madrid, 28049 Madrid, Spain.
authors.forename: Jorgina
authors.initials: J
authors.lastname: Satrústegui
authors.affiliation: From the Department of Biochemistry.
authors.forename: Mark
authors.initials: M
authors.lastname: Kanow
authors.affiliation: Bernard and Shirlee Brown Glaucoma Laboratory and Barbara and Donald Jonas Stem Cell Laboratory, Department of Ophthalmology, Columbia University, New York, New York, and.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.affiliation: Bernard and Shirlee Brown Glaucoma Laboratory and Barbara and Donald Jonas Stem Cell Laboratory, Department of Ophthalmology, Columbia University, New York, New York, and Department of Pathology and Cell Biology and Institute of Human Nutrition, Columbia University, New York, New York 10032.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.affiliation: Diabetes and Obesity Center of Excellence.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
authors.affiliation: From the Department of Biochemistry, Department of Ophthalmology, University of Washington, Seattle, Washington 98109, jbhhh@uw.edu.
authors.forename: James B
authors.initials: JB
authors.lastname: Hurley
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D020013:Calcium Signaling / Q000528:radiation effects*; D002952:Citric Acid Cycle / Q000528:radiation effects; D006152:Cyclic GMP / Q000378:metabolism; D004579:Electron Transport / Q000528:radiation effects; D004734:Energy Metabolism / Q000528:radiation effects*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis / Q000528:radiation effects; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008027:Light; D055537:Light Signal Transduction; D055442:Metabolome / Q000528:radiation effects; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000528:radiation effects; D012160:Retina / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D046509:Tissue Culture Techniques; D015293:Transducin / Q000235:genetics / Q000378:metabolism*
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D017920:Antiporters; D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; C515337:Gnat2 protein, mouse; C051046:aspartate-glutamate carrier; D007655:Ketoglutarate Dehydrogenase Complex; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin; D006152:Cyclic GMP
keywords: anaerobic metabolism; calcium; mitochondria; photoreceptor; phototransduction; retina