Flow of energy in the outer retina in darkness and in light.
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.
Linton
Jonathan D
JD
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. jbhhh@u.washington.edu
Holzhausen
Lars C
LC
Babai
Norbert
N
Song
Hongman
H
Miyagishima
Kiyoharu J
KJ
Stearns
George W
GW
Lindsay
Ken
K
Wei
Junhua
J
Chertov
Andrei O
AO
Peters
Theo A
TA
Caffe
Romeo
R
Pluk
Helma
H
Seeliger
Mathias W
MW
Tanimoto
Naoyuki
N
Fong
Kimberly
K
Bolton
Laura
L
Kuok
Denise L T
DL
Sweet
Ian R
IR
Bartoletti
Theodore M
TM
Radu
Roxana A
RA
Travis
Gabriel H
GH
Zagotta
Willam N
WN
Townes-Anderson
Ellen
E
Parker
Ed
E
Van der Zee
Catharina E E M
CE
Sampath
Alapakkam P
AP
Sokolov
Maxim
M
Thoreson
Wallace B
WB
Hurley
James B
JB
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
D005971:Glutamates; D047428:Protein Kinase Inhibitors; D004139:Dinitrofluorobenzene; D003402:Creatine Kinase
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