Flow of energy in the outer retina in darkness and in light

• DOI: 10.1073/pnas.1002471107
• Publication Date: 2010-05-06T02:53:50Z
• Authors: Jonathan D. Linton; Lars C. Holzhausen; Norbert Babai; Hongman Song; Kiyoharu J. Miyag...; George W. Stearns; Ken Lindsay; Junhua Wei; Andrei O. Chertov; Theo A. Peters; Romeo Caffe; Helma Pluk; Mathias W. Seeliger; Naoyuki Tanimoto; Kimberly Fong; Laura Bolton; Denise L. T. Kuok; Ian R. Sweet; Theodore M. Barto...; Roxana A. Radu; Gabriel H. Travis; Willam N. Zagotta; Ellen Townes-Ande...; Ed Parker; Catharina E. E. M...; Alapakkam P. Sampath; Maxim Sokolov; Wallace B. Thoreson; James B. Hurley
• Keywords: 0301 basic medicine; DCN 2: Functional Neurogenomics; Presynaptic Terminals; Retinal Vessels; Urodela; Darkness; NCMLS 6: Genetics and epigenetic pathways of disease; Retinal Photoreceptor Cell Outer Segment; Models, Biological; Synaptic Transmission; Retina; Mitochondria; Mice; 03 medical and health sciences; Glutamates; Electroretinography; Retinal Cone Photoreceptor Cells; NCMLS 4: Energy and redox metabolism; Animals; Dinitrofluorobenzene; Energy Metabolism; Creatine Kinase; Protein Kinase Inhibitors

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.