title: Flow of energy in the outer retina in darkness and in light.
abstract: Structural features of neurons create challenges for effective production and distribution of essential metabolic energy. We investigated how metabolic energy is distributed between cellular compartments in photoreceptors. In avascular retinas, aerobic production of energy occurs only in mitochondria that are located centrally within the photoreceptor. Our findings indicate that metabolic energy flows from these central mitochondria as phosphocreatine toward the photoreceptor's synaptic terminal in darkness. In light, it flows in the opposite direction as ATP toward the outer segment. Consistent with this model, inhibition of creatine kinase in avascular retinas blocks synaptic transmission without influencing outer segment activity. Our findings also reveal how vascularization of neuronal tissue can influence the strategies neurons use for energy management. In vascularized retinas, mitochondria in the synaptic terminals of photoreceptors make neurotransmission less dependent on creatine kinase. Thus, vasculature of the tissue and the intracellular distribution of mitochondria can play key roles in setting the strategy for energy distribution in neurons.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. jbhhh@u.washington.edu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Linton
authors.forename: Lars C
authors.initials: LC
authors.lastname: Holzhausen
authors.forename: Norbert
authors.initials: N
authors.lastname: Babai
authors.forename: Hongman
authors.initials: H
authors.lastname: Song
authors.forename: Kiyoharu J
authors.initials: KJ
authors.lastname: Miyagishima
authors.forename: George W
authors.initials: GW
authors.lastname: Stearns
authors.forename: Ken
authors.initials: K
authors.lastname: Lindsay
authors.forename: Junhua
authors.initials: J
authors.lastname: Wei
authors.forename: Andrei O
authors.initials: AO
authors.lastname: Chertov
authors.forename: Theo A
authors.initials: TA
authors.lastname: Peters
authors.forename: Romeo
authors.initials: R
authors.lastname: Caffe
authors.forename: Helma
authors.initials: H
authors.lastname: Pluk
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Kimberly
authors.initials: K
authors.lastname: Fong
authors.forename: Laura
authors.initials: L
authors.lastname: Bolton
authors.forename: Denise L T
authors.initials: DL
authors.lastname: Kuok
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Bartoletti
authors.forename: Roxana A
authors.initials: RA
authors.lastname: Radu
authors.forename: Gabriel H
authors.initials: GH
authors.lastname: Travis
authors.forename: Willam N
authors.initials: WN
authors.lastname: Zagotta
authors.forename: Ellen
authors.initials: E
authors.lastname: Townes-Anderson
authors.forename: Ed
authors.initials: E
authors.lastname: Parker
authors.forename: Catharina E E M
authors.initials: CE
authors.lastname: Van der Zee
authors.forename: Alapakkam P
authors.initials: AP
authors.lastname: Sampath
authors.forename: Maxim
authors.initials: M
authors.lastname: Sokolov
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: James B
authors.initials: JB
authors.lastname: Hurley
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003624:Darkness; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004596:Electroretinography; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005971:Glutamates / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D008954:Models, Biological; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D055214:Retinal Photoreceptor Cell Outer Segment / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000528:radiation effects; D014562:Caudata / Q000502:physiology
chemical_list: D005971:Glutamates; D047428:Protein Kinase Inhibitors; D004139:Dinitrofluorobenzene; D003402:Creatine Kinase
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