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BioMed Research International
Volume 2014 (2014), Article ID 472459, 22 pages
http://dx.doi.org/10.1155/2014/472459
Review Article

Fatty Acids in Energy Metabolism of the Central Nervous System

1Institute of Molecular Biology and Biophysics, Siberian Division of the Russian Academy of Medical Sciences (SB RAMS), 2 Timakova st., Novosibirsk 630117, Russia
2Department of Surgery, Drexel University College of Medicine, Philadelphia, PA, USA

Received 2 February 2014; Revised 29 March 2014; Accepted 29 March 2014; Published 4 May 2014

Academic Editor: Ancha Baranova

Copyright © 2014 Alexander Panov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. C. Wallace, “A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine,” Annual Review of Genetics, vol. 39, pp. 359–407, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. J. P. Jenuth, A. C. Peterson, K. Fu, and E. A. Shoubridge, “Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA,” Nature Genetics, vol. 14, no. 2, pp. 146–151, 1996. View at Publisher · View at Google Scholar · View at Scopus
  3. D. C. Wallace, “Why do we still have a maternally inherited mitochondrial DNA? insights from evolutionary medicine,” Annual Review of Biochemistry, vol. 76, pp. 781–821, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. D. C. Wallace, “Mitochondria as Chi,” Genetics, vol. 179, no. 2, pp. 727–735, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. K. Darvishi, S. Sharma, A. K. Bhat, E. Rai, and R. N. K. Bamezai, “Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer,” Cancer Letters, vol. 249, no. 2, pp. 249–255, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. R.-K. Bai, S. M. Leal, D. Covarrubias, A. Liu, and L.-J. C. Wong, “Mitochondrial genetic background modifies breast cancer risk,” Cancer Research, vol. 67, no. 10, pp. 4687–4694, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. L. M. Booker, G. M. Habermacher, B. C. Jessie et al., “North American white mitochondrial haplogroups in prostate and renal cancer,” Journal of Urology, vol. 175, no. 2, pp. 468–472, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Brandon, P. Baldi, and D. C. Wallace, “Mitochondrial mutations in cancer,” Oncogene, vol. 25, no. 34, pp. 4647–4662, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Panov, S. Dikalov, N. Shalbuyeva, R. Hemendinger, J. T. Greenamyre, and J. Rosenfeld, “Species- and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice,” American Journal of Physiology—Cell Physiology, vol. 292, no. 2, pp. C708–C718, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Panov, P. Schonfeld, S. Dikalov, R. Hemendinger, H. L. Bonkovsky, and B. R. Brooks, “The neuromediator glutamate, through specific substrate interactions, enhances mitochondrial ATP production and reactive oxygen species generation in nonsynaptic brain mitochondria,” The Journal of Biological Chemistry, vol. 284, no. 21, pp. 14448–14456, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Panov, Practical Mitochondriology. Pitfalls and Problems in Studies of Mitochondria, Amazon, Lexington, Ky, USA, 2013.
  12. A. Panov and S. Dikalov, “Structural and metabolic determinants of mitochondrial superoxide and detection methods of mitochondrial superoxide and hydrogen peroxide,” in Mitochondria in Health and Death, chapter 5, Elsevier, 2014. View at Google Scholar
  13. N. A. Campbell, B. Williamson, and R. J. Hyden, Biology: Exploring Life, Pearson Prentice Hall, Boston, Mass, USA, 2006.
  14. A. V. Panov, Y. M. Konstantinov, and V. V. Lyakhovich, “The possible role of palmitoyl CoA in the regulation of the adenine nucleotides transport in mitochondria under different metabolic states. I. Comparison of liver mitochondria from starved and fed rats,” Journal of Bioenergetics, vol. 7, no. 2, pp. 75–85, 1975. View at Google Scholar · View at Scopus
  15. A. V. Panov, V. A. Vavilin, V. N. Solovyov, and V. V. Lyakhovich, “Relationships between the adenine nucleotide system and oxidative phosphorylation in rat liver in the dynamics of starvation,” Biokhimiya, vol. 48, no. 2, pp. 235–243, 1983. View at Google Scholar · View at Scopus
  16. A. V. Panov, N. Kubalik, N. Zinchenko et al., “Metabolic and functional differences between brain and spinal cord mitochondria underlie different predisposition to pathology,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 300, no. 4, pp. R844–R854, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. T. R. Kasser, A. Deutch, and R. J. Martin, “Uptake and utilization of metabolites in specific brain sites relative to feeding status,” Physiology and Behavior, vol. 36, no. 6, pp. 1161–1165, 1986. View at Google Scholar · View at Scopus
  18. N. J. Abbott, L. Rönnbäck, and E. Hansson, “Astrocyte-endothelial interactions at the blood-brain barrier,” Nature Reviews Neuroscience, vol. 7, pp. 41–53, 2006. View at Google Scholar
  19. N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiology of Disease, vol. 37, no. 1, pp. 13–25, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Ballabh, A. Braun, and M. Nedergaard, “The blood-brain barrier: an overview: structure, regulation, and clinical implications,” Neurobiology of Disease, vol. 16, no. 1, pp. 1–13, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. D. Virgintino, P. Monaghan, D. Robertson et al., “An immunohistochemical and morphometric study on astrocytes and microvasculature in the human cerebral cortex,” The Histochemical Journal, vol. 29, no. 9, pp. 655–660, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Nag and D. J. Begley, “Blood-brain barrier, exchange of metabolites and gases,” in Pathology and Genetics. Cerebrovascular Diseases, H. Kalimo, Ed., pp. 22–29, Neuropath Press, Basel, Switzerland, 2005. View at Google Scholar
  23. T. K. T. Lam, G. J. Schwartz, and L. Rossetti, “Hypothalamic sensing of fatty acids,” Nature Neuroscience, vol. 8, no. 5, pp. 579–584, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. R. S. el-Bacha and A. Minn, “Drug metabolizing enzymes in cerebrovascular endothelial cells afford a metabolic protection to the brain,” Cellular and Molecular Biology, vol. 45, no. 1, pp. 15–23, 1999. View at Google Scholar · View at Scopus
  25. N. Bresolin, L. Freddo, L. Vergani, and C. Angelini, “Carnitine, carnitine acyltransferases, and rat brain function,” Experimental Neurology, vol. 78, no. 2, pp. 285–292, 1982. View at Google Scholar · View at Scopus
  26. P. Ciofi, M. Garret, O. Lapirot et al., “Brain-endocrine interactions: a microvascular route in the mediobasal hypothalamus,” Endocrinology, vol. 150, no. 12, pp. 5509–5519, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. K. E. Schlageter, P. Molnar, G. D. Lapin, and D. R. Groothuis, “Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties,” Microvascular Research, vol. 58, no. 3, pp. 312–328, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. G. A. Dienel and L. Hertz, “Glucose and lactate metabolism during brain activation,” Journal of Neuroscience Research, vol. 66, no. 5, pp. 824–838, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. C.-P. Chih, P. Lipton, and E. L. Roberts Jr., “Do active cerebral neurons really use lactate rather than glucose?” Trends in Neurosciences, vol. 24, no. 10, pp. 573–578, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. C.-P. Chi and E. L. Roberts Jr., “Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis,” Journal of Cerebral Blood Flow and Metabolism, vol. 23, no. 11, pp. 1263–1281, 2003. View at Google Scholar · View at Scopus
  31. L. Hertz, “The astrocyte-neuron lactate shuttle: a challenge of a challenge,” Journal of Cerebral Blood Flow and Metabolism, vol. 24, no. 11, pp. 1241–1248, 2004. View at Google Scholar · View at Scopus
  32. L. Pellerin and P. J. Magistretti, “Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 22, pp. 10625–10629, 1994. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Pellerin and P. J. Magistretti, “Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+ ATPase,” Developmental Neuroscience, vol. 18, no. 5-6, pp. 336–342, 1996. View at Google Scholar · View at Scopus
  34. P. J. Magistretti and L. Pellerin, “Metabolic coupling during activation: a cellular view,” Advances in Experimental Medicine and Biology, vol. 413, pp. 161–166, 1997. View at Google Scholar · View at Scopus
  35. L. Pellerin, “Lactate as a pivotal element in neuron-glia metabolic cooperation,” Neurochemistry International, vol. 43, no. 4-5, pp. 331–338, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. L. Pellerin and P. J. Magistretti, “Empiricism and rationalism: two paths toward the same goal,” Journal of Cerebral Blood Flow and Metabolism, vol. 24, no. 11, pp. 1240–1241, 2004. View at Google Scholar · View at Scopus
  37. L. Pellerin and P. J. Magistretti, “Neuroenergetics: calling upon astrocytes to satisfy hungry neurons,” Neuroscientist, vol. 10, no. 1, pp. 53–62, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Pellerin, A. P. Halestrap, and K. Pierre, “Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain,” Journal of Neuroscience Research, vol. 79, no. 1-2, pp. 55–64, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. L. Pellerin, A.-K. Bouzier-Sore, A. Aubert et al., “Activity-dependent regulation of energy metabolism by astrocytes: an update,” Glia, vol. 55, no. 12, pp. 1251–1262, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Schousboe, L. K. Bak, and H. S. Waagepetersen, “Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA,” Frontiers in Endocrinology, vol. 4, no. 102, pp. 1–11, 2013. View at Google Scholar
  41. L. Pellerin and P. J. Magistretti, “Sweet sixteen for ANLS,” Journal Cerebral Blood Flow Metabolism, vol. 32, pp. 1152–1166, 2012. View at Google Scholar
  42. A. -K. Bouzier-Sore and L. Pellerin, “Unraveling the complex, metabolic nature of astrocytes,” Frontiers in Cellular Neuroscience, vol. 7, article 179, pp. 1–13, 2013. View at Google Scholar
  43. G. A. Dienel and N. F. Cruz, “Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought?” Neurochemistry International, vol. 45, no. 2-3, pp. 321–351, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. G. A. Dienel, “Brain lactate metabolism: the discoveries and the controversies,” Journal of Cerebral Blood Flow and Metabolism, vol. 32, pp. 1107–1138, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. D. A. Berkich, M. S. Ola, J. Cole, A. J. Sweatt, S. M. Hutson, and K. F. LaNoue, “Mitochondrial transport proteins of the brain,” Journal of Neuroscience Research, vol. 85, no. 15, pp. 3367–3377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. L. Contreras, A. Urbieta, K. Kobayashi, T. Saheki, and J. Satrústegui, “Low levels of citrin (SLC25A13) expression in adult mouse brain restricted to neuronal clusters,” Journal of Neuroscience Research, vol. 88, no. 5, pp. 1009–1016, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Itoh, T. Esaki, K. Shimoji et al., “Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 8, pp. 4879–4884, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. L. Sokoloff, S. Takahashi, J. Gotoh, B. F. Driscoll, and M. J. Law, “Contribution of astroglia to functionally activated energy metabolism,” Developmental Neuroscience, vol. 18, no. 5-6, pp. 343–352, 1996. View at Google Scholar · View at Scopus
  49. A. Tarozzi, F. Morroni, C. Bolondi et al., “Neuroprotective effects of erucin against 6-hydroxydopamine-induced oxidative damage in a dopaminergic-like neuroblastoma cell line,” International Journal of Molecular Sciences, vol. 13, no. 9, pp. 10899–10910, 2012. View at Google Scholar
  50. A. Panov and Z. Orynbayeva, “Bioenergetic and antiapoptotic properties of mitochondria from cultured human prostate cancer cell lines PC-3, DU145 and LNCaP,” PloS ONE, vol. 8, no. 8, Article ID e72078, 2013. View at Google Scholar
  51. G. A. Dhopeshwarkar and J. F. Mead, “Fatty acid uptake by the brain. III. Incorporation of [I-14C]oleic acid into the adult ratbrain,” Biochimica et Biophysica Acta, vol. 210, no. 2, pp. 250–256, 1970. View at Google Scholar · View at Scopus
  52. G. A. Dhopeshwarkar, C. Subramanian, and J. F. Mead, “Fatty acid uptake by the brain V. incorporation of [1-14c]linolenic acid into adult rat brain,” Biochimica et Biophysica Acta, vol. 239, no. 2, pp. 162–167, 1971. View at Google Scholar · View at Scopus
  53. C. Allweis, T. Landau, M. Abeles, and J. Magnes, “The oxidation of uniformly labelled albumin-bound palmitic acid to CO2 by the perfused cat brain,” The Journal of Neurochemistry, vol. 13, no. 9, pp. 795–804, 1966. View at Google Scholar · View at Scopus
  54. J. J. Spitzer, “CNS and fatty acid metabolism,” Physiologist, vol. 16, no. 1, pp. 55–68, 1973. View at Google Scholar · View at Scopus
  55. J. B. Warshaw and M. L. Terry, “Cellular energy metabolism during fetal development. VI. Fatty acid oxidation by developing brain,” Developmental Biology, vol. 52, no. 1, pp. 161–166, 1976. View at Google Scholar · View at Scopus
  56. D. Ebert, R. G. Haller, and M. E. Walton, “Energy contribution of octanoate to intact rat brain metabolism measured by13C nuclear magnetic resonance spectroscopy,” The Journal of Neuroscience, vol. 23, no. 13, pp. 5928–5935, 2003. View at Google Scholar · View at Scopus
  57. K. A. Nałȩcz, D. Miecz, V. Berezowski, and R. Cecchelli, “Carnitine: transport and physiological functions in the brain,” Molecular Aspects of Medicine, vol. 25, no. 5-6, pp. 551–567, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. B. Pardo B, L. Contreras, and J. Satrústegui, “De novo synthesis of glial glutamate and glutamine in young mice requires aspartate provided by the neuronal mitochondrial aspartate-glutamate carrier aralar/AGC1,” Frontiers in Endocrinology, vol. 4, article 149, pp. 1–4, 2013. View at Google Scholar
  59. L. Hertz, “The glutamate-glutamine (GABA) cycle: importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation,” Frontiers in Endocrinology, vol. 4, p. 59, 2013. View at Google Scholar
  60. M. Yudkoff, D. Nelson, Y. Daikhin, and M. Erecinska, “Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle,” The Journal of Biological Chemistry, vol. 269, no. 44, pp. 27414–27420, 1994. View at Google Scholar · View at Scopus
  61. N. J. K. Tillakaratne, L. Medina-Kauwe, and K. M. Gibson, “Gamma-aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues,” Comparative Biochemistry and Physiology A: Physiology, vol. 112, no. 2, pp. 247–263, 1995. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Panov, N. Steuerwald, V. Vavilin et al., “Role of neuronal mitochondrial metabolic phenotype in pathogenesis of ALS,” in Amyotrophic Lateral Sclerosis, M. H. Maurer, Ed., chapter 6, INTECH Open Access Publisher, 2012. View at Google Scholar
  63. M. Abeles, Corticonics: Neural Circuits of the Cerebral Cortex, Cambridge University Press, New York, NY, USA, 1991.
  64. M. T. T. Wong-Riley, “Cytochrome oxidase: an endogenous metabolic marker for neuronal activity,” Trends in Neurosciences, vol. 12, no. 3, pp. 94–101, 1989. View at Google Scholar · View at Scopus
  65. A. Bignami, “Glial cells in thew central nerve system,” in Discussions in Neuroscience, P. J. Magistretti, Ed., vol. 8, pp. 1–45, Elsevier, Amsterdam, 1991. View at Google Scholar
  66. S. Herculano-Houzel, “Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution,” PLoS ONE, vol. 6, no. 3, Article ID e17514, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Sokoloff, S. Takahashi, J. Gotoh, B. F. Driscoll, and M. J. Law, “Contribution of astroglia to functionally activated energy metabolism,” Developmental Neuroscience, vol. 18, no. 5-6, pp. 343–352, 1996. View at Google Scholar · View at Scopus
  68. M. C. McKenna, I. B. Hopkins, S. L. Lindauer, and P. Bamford, “Aspartate aminotransferase in synaptic and nonsynaptic mitochondria: differential effect of compounds that influence transient hetero-enzyme complex (metabolon) formation,” Neurochemistry International, vol. 48, no. 6-7, pp. 629–636, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. D. Attwell and S. B. Laughlin, “An energy budget for signaling in the grey matter of the brain,” Journal of Cerebral Blood Flow and Metabolism, vol. 21, no. 10, pp. 1133–1145, 2001. View at Google Scholar · View at Scopus
  70. C. Morland, S. Henjum, E. G. Iversen, K. K. Skrede, and B. Hassel, “Evidence for a higher glycolytic than oxidative metabolic activity in white matter of rat brain,” Neurochemistry International, vol. 50, no. 5, pp. 703–709, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. L. Sokoloff, “Energetics of functional activation in neural tissues,” Neurochemical Research, vol. 24, no. 2, pp. 321–329, 1999. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Poritsky, “Two and three dimenstional ultrastructure of boutons and glial cells on the motoneuronal surface in the cat spinal cord,” The Journal of Comparative Neurology, vol. 135, no. 4, pp. 423–452, 1969. View at Google Scholar · View at Scopus
  73. T. Holtzman, T. Rajapaksa, A. Mostofi, and S. A. Edgley, “Different responses of rat cerebellar Purkinje cells and Golgi cells evoked by widespread convergent sensory inputs,” The Journal of Physiology, vol. 574, part 2, pp. 491–507, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. A. V. Panov and R. C. Scaduto Jr., “Substrate specific effects of calcium on metabolism of rat heart mitochondria,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 270, no. 4, pp. H1398–H1406, 1996. View at Google Scholar · View at Scopus
  75. D. Lovatt, U. Sonnewald, H. S. Waagepetersen et al., “The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex,” The Journal of Neuroscience, vol. 27, no. 45, pp. 12255–12266, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. N. C. Danbolt, “Glutamate uptake,” Progress in Neurobiology, vol. 65, no. 1, pp. 1–105, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. D. N. Furness, Y. Dehnes, A. Q. Akhtar et al., “A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2),” Neuroscience, vol. 157, no. 1, pp. 80–94, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. N. R. Sibson, A. Dhankhar, G. F. Mason, D. L. Rothman, K. L. Behar, and R. G. Shulman, “Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 1, pp. 316–321, 1998. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Dehnes, F. A. Chaudhry, K. Ullensvang, K. P. Lehre, J. Storm-Mathisen, and N. C. Danbolt, “The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia,” The Journal of Neuroscience, vol. 18, no. 10, pp. 3606–3619, 1998. View at Google Scholar · View at Scopus
  80. G. Brasnjo and T. S. Otis, “Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber-Purkinje cell synapse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 16, pp. 6273–6278, 2004. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Auger and D. Attwell, “Fast removal of synaptic glutamate by postsynaptic transporters,” Neuron, vol. 28, no. 2, pp. 547–558, 2000. View at Google Scholar · View at Scopus
  82. A. Massie, L. Cnops, I. Smolders et al., “High-affinity Na+/K+-dependent glutamate transporter EAAT4 is expressed throughout the rat fore- and midbrain,” The Journal of Comparative Neurology, vol. 511, no. 2, pp. 155–172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. Z. Li, K.-I. Okamoto, Y. Hayashi, and M. Sheng, “The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses,” Cell, vol. 119, no. 6, pp. 873–887, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. D. G. Nicholls, “The glutamatergic nerve terminal,” European Journal of Biochemistry, vol. 212, no. 3, pp. 613–631, 1993. View at Google Scholar · View at Scopus
  85. L. K. Bak, A. Schousboe, and H. S. Waagepetersen, “The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer,” The Journal of Neurochemistry, vol. 98, no. 3, pp. 641–653, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. F. Conti, A. Minelli, and M. Melone, “GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications,” Brain Research Reviews, vol. 45, no. 3, pp. 196–212, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. M. He, Z. Pei, A.-W. Mohsen et al., “Identification and characterization of new long chain Acyl-CoA dehydrogenases,” Molecular Genetics and Metabolism, vol. 102, no. 4, pp. 418–429, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Genoud, C. Quairiaux, P. Steiner, H. Hirling, E. Welker, and G. W. Knott, “Plasticity of astrocytic coverage and glutamate transporter expression in adult mouse cortex,” PLoS Biology, vol. 4, no. 11, p. e343, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. N. M. Rowley, K. K. Madsen, A. Schousboe, and H. Steve White, “Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control,” Neurochemistry International, vol. 61, pp. 546–558, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Martinez Hernandez, K. P. Bell, and M. D. Norenberg, “Glutamine synthetase: glial localization in brain,” Science, vol. 195, no. 4284, pp. 1356–1358, 1977. View at Google Scholar · View at Scopus
  91. M. D. Norenberg and A. Martinez-Hernandez, “Fine structural localization of glutamine synthetase in astrocytes of rat brain,” Brain Research, vol. 161, no. 2, pp. 303–310, 1979. View at Publisher · View at Google Scholar · View at Scopus
  92. M. D. Norenberg, “The distribution of glutamine synthetase in the rat central nervous system,” Journal of Histochemistry and Cytochemistry, vol. 27, no. 3, pp. 756–762, 1979. View at Google Scholar · View at Scopus
  93. P. J. Magistretti and L. Pellerin, “Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 354, no. 1387, pp. 1155–1163, 1999. View at Google Scholar · View at Scopus
  94. M. C. McKenna, J. H. Stevenson, X. Huang, and I. B. Hopkins, “Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals,” Neurochemistry International, vol. 37, no. 2-3, pp. 229–241, 2000. View at Publisher · View at Google Scholar · View at Scopus
  95. M. C. McKenna, “The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain,” Journal of Neuroscience Research, vol. 85, no. 15, pp. 3347–3358, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. B. Pardo, T. B. Rodrigues, L. Contreras et al., “Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation,” Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 1, pp. 90–101, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. R. Dringen, R. Gebhardt, and B. Hamprecht, “Glycogen in astrocytes: possible function as lactate supply for neighboring cells,” Brain Research, vol. 623, no. 2, pp. 208–214, 1993. View at Publisher · View at Google Scholar · View at Scopus
  98. G. A. Dienel, R. Y. Wang, and N. F. Cruz, “Generalized sensory stimulation of conscious rats increases labeling of oxidative pathways of glucose metabolism when the brain glucose-oxygen uptake ratio rises,” Journal of Cerebral Blood Flow and Metabolism, vol. 22, no. 12, pp. 1490–1502, 2002. View at Google Scholar · View at Scopus
  99. A.-K. Bouzier-Sore, P. Voisin, P. Canioni, P. J. Magistretti, and L. Pellerin, “Lactate is a preferential oxidative energy substrate over glucose for neurons in culture,” Journal of Cerebral Blood Flow and Metabolism, vol. 23, no. 11, pp. 1298–1306, 2003. View at Google Scholar · View at Scopus
  100. R. P. Shank, G. S. Bennett, S. O. Freytag, and G. Campbell, “Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools,” Brain Research, vol. 329, no. 1-2, pp. 364–367, 1985. View at Google Scholar · View at Scopus
  101. A. C. H. Yu, J. Drejer, L. Hertz, and A. Schousboe, “Pyruvate carboxylase activity in primary cultures of astrocytes and neurons,” The Journal of Neurochemistry, vol. 41, no. 5, pp. 1484–1487, 1983. View at Google Scholar · View at Scopus
  102. H. S. Waagepetersen, H. Qu, A. Schousboe, and U. Sonnewald, “Elucidation of the quantitative significance of pyruvate carboxylation in cultured cerebellar neurons and astrocytes,” Journal of Neuroscience Research, vol. 66, no. 5, pp. 763–770, 2001. View at Publisher · View at Google Scholar · View at Scopus
  103. N. D. Halim, T. Mcfate, A. Mohyeldin et al., “Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons,” Glia, vol. 58, no. 10, pp. 1168–1176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. M. C. McKenna, J. H. Stevenson, X. Huang, and I. B. Hopkins, “Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals,” Neurochemistry International, vol. 37, no. 2-3, pp. 229–241, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Bröer, J. W. Deitmer, and S. Bröer, “Astroglial glutamine transport by system N is upregulated by glutamate,” Glia, vol. 48, no. 4, pp. 298–310, 2004. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Loaiza, O. H. Porras, and L. F. Barros, “Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy,” The Journal of Neuroscience, vol. 23, no. 19, pp. 7337–7342, 2003. View at Google Scholar · View at Scopus
  107. O. H. Porras, A. Loaiza, and L. Felipe Barros, “Glutamate mediates acute glucose transport inhibition in hippocampal neurons,” The Journal of Neuroscience, vol. 24, no. 43, pp. 9669–9673, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. S. J. Vannucci, F. Maher, and I. A. Simpson, “Glucose transporter proteins in brain: delivery of glucose to neurons and glia,” Glia, vol. 21, no. 1, pp. 2–21, 1997. View at Google Scholar
  109. D. L. Needels and J. E. Wilson, “The identity of hexokinase activities from mitochondrial and cytoplasmic fractions of rat brain homogenates,” The Journal of Neurochemistry, vol. 40, no. 4, pp. 1134–1143, 1983. View at Google Scholar · View at Scopus
  110. L. D. Griffin, B. D. Gelb, V. Adams, and E. R. B. McCabe, “Developmental expression of hexokinase 1 in the rat,” Biochimica et Biophysica Acta—Gene Structure and Expression, vol. 1129, no. 3, pp. 309–317, 1992. View at Publisher · View at Google Scholar · View at Scopus
  111. R. M. Lynch, K. E. Fogarty, and F. S. Fay, “Modulation of hexokinase association with mitochondria analyzed with quantitative three-dimensional confocal microscopy,” The Journal of Cell Biology, vol. 112, no. 3, pp. 385–395, 1991. View at Publisher · View at Google Scholar · View at Scopus
  112. S. Nagamatsu, Y. Nakamichi, N. Inoue, M. Inoue, H. Nishino, and H. Sawa, “Rat C6 glioma cell growth is related to glucose transport and metabolism,” Biochemical Journal, vol. 319, no. 2, pp. 477–482, 1996. View at Google Scholar · View at Scopus
  113. L. Hertz and H. R. Zielke, “Astrocytic control of glutamatergic activity: astrocytes as stars of the show,” Trends in Neurosciences, vol. 27, no. 12, pp. 735–743, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. N. C. Danbolt, “Glutamate uptake,” Progress in Neurobiology, vol. 65, no. 1, pp. 1–105, 2001. View at Publisher · View at Google Scholar · View at Scopus
  115. P. J. Randle, “Fuel selection in animals,” Biochemical Society Transactions, vol. 14, no. 5, pp. 799–806, 1986. View at Google Scholar · View at Scopus
  116. A. Adina-Zada, T. N. Zeczycki, and P. V. Attwood, “Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA,” Archives of Biochemistry and Biophysics, vol. 519, no. 2, pp. 118–130, 2012. View at Publisher · View at Google Scholar · View at Scopus
  117. N. R. Sims, “Rapid isolation of metabolically active mitochondria from rat brain and subregions using percoll density gradient centrifugation,” The Journal of Neurochemistry, vol. 55, no. 2, pp. 698–707, 1990. View at Google Scholar · View at Scopus
  118. M. Ramos, A. del Arco, B. Pardo et al., “Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord,” Developmental Brain Research, vol. 143, no. 1, pp. 33–46, 2003. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. Xu, M. S. Ola, D. A. Berkich et al., “Energy sources for glutamate neurotransmission in the retina: absence of the aspartate/glutamate carrier produces reliance on glycolysis in glia,” The Journal of Neurochemistry, vol. 101, no. 1, pp. 120–131, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. M. C. McKenna, H. S. Waagepetersen, A. Schousboe, and U. Sonnewald, “Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools,” Biochemical Pharmacology, vol. 71, no. 4, pp. 399–407, 2006. View at Publisher · View at Google Scholar · View at Scopus
  121. K. F. LaNoue and A. C. Schoolwerth, “Metabolite transport in mitochondria,” Annual Review of Biochemistry, vol. 48, pp. 871–922, 1979. View at Google Scholar · View at Scopus
  122. F. Palmieri, “The mitochondrial transporter family (SLC25): physiological and pathological implications,” Pflugers Archiv European Journal of Physiology, vol. 447, no. 5, pp. 689–709, 2004. View at Publisher · View at Google Scholar · View at Scopus
  123. G. Fiermonte, L. Palmieri, S. Todisco, G. Agrimi, F. Palmieri, and J. E. Walker, “Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms,” The Journal of Biological Chemistry, vol. 277, no. 22, pp. 19289–19294, 2002. View at Publisher · View at Google Scholar · View at Scopus
  124. T. S. Otis, M. P. Kavanaugh, and C. E. Jahr, “Postsynaptic glutamate transport at the climbing fiber-Purkinje cell synapse,” Science, vol. 277, no. 5331, pp. 1515–1518, 1997. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Panov, N. Kubalik, N. Zinchenko, R. Hemendinger, S. Dikalov, and H. L. Bonkovsky, “Respiration and ROS production in brain and spinal cord mitochondria of transgenic rats with mutant G93a Cu/Zn-superoxide dismutase gene,” Neurobiology of Disease, vol. 44, no. 1, pp. 53–62, 2011. View at Publisher · View at Google Scholar · View at Scopus
  126. A. V. Panov, V. A. Vavilin, V. V. Lyakhovich, B. R. Brooks, and H. L. Bonkovsky, “Effect of bovine serum albumin on mitochondrial respiration in the brain and liver of mice and rats,” Bulletin of Experimental Biology and Medicine, vol. 149, no. 2, pp. 187–190, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. S. I. Dikalov, M. P. Vitek, and R. P. Mason, “Cupric-amyloid β peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical,” Free Radical Biology and Medicine, vol. 36, no. 3, pp. 340–347, 2004. View at Publisher · View at Google Scholar · View at Scopus
  128. B. A. C. Ackrell, E. B. Kearney, and D. Edmondson, “Mechanism of the reductive activation of succinate dehydrogenase,” The Journal of Biological Chemistry, vol. 250, no. 18, pp. 7114–7119, 1975. View at Google Scholar · View at Scopus
  129. A. D. Vinogradov, D. Winter, and T. E. King, “The binding site for oxaloacetate on succinate dehydrogenase,” Biochemical and Biophysical Research Communications, vol. 49, no. 2, pp. 441–444, 1972. View at Google Scholar · View at Scopus
  130. B. A. C. Ackrell, E. B. Kearney, and M. Mayr, “Role of oxalacetate in the regulation of mammalian succinate dehydrogenase,” The Journal of Biological Chemistry, vol. 249, no. 7, pp. 2021–2027, 1974. View at Google Scholar · View at Scopus
  131. D. E. Bergles, J. S. Diamond, and C. E. Jahr, “Clearance of glutamate inside the synapse and beyond,” Current Opinion in Neurobiology, vol. 9, no. 3, pp. 293–298, 1999. View at Publisher · View at Google Scholar · View at Scopus
  132. M. Ruscak, J. Orlicky, V. Zubor, and H. Hager, “Alanine aminotransferase in bovine brain: purification and properties,” The Journal of Neurochemistry, vol. 39, no. 1, pp. 210–216, 1982. View at Google Scholar · View at Scopus
  133. C. J. Stanley and R. N. Perham, “Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method,” Biochemical Journal, vol. 191, no. 1, pp. 147–154, 1980. View at Google Scholar · View at Scopus
  134. E. A. Lopez-Beltran, M. J. Mate, and S. Cerdan, “Dynamics and environment of mitochondrial water as detected by 1H NMR,” Journal Biological Chemistry, vol. 271, pp. 10648–10653, 1996. View at Google Scholar
  135. J. Angdisen, V. D. G. Moore, J. M. Cline, R. M. Payne, and J. A. Ibdah, “Mitochondrial trifunctional protein defects: molecular basis and novel therapeutic approaches,” Current Drug Targets: Immune, Endocrine and Metabolic Disorders, vol. 5, no. 1, pp. 27–40, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. K. F. LaNoue, J. Bryla, and J. R. Williamson, “Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria,” The Journal of Biological Chemistry, vol. 247, no. 3, pp. 667–679, 1972. View at Google Scholar · View at Scopus
  137. K. F. LaNoue and J. R. Williamson, “Interrelationships between malate-aspartate shuttle and citric acid cycle in rat heart mitochondria,” Metabolism, vol. 20, no. 2, pp. 119–140, 1971. View at Google Scholar · View at Scopus
  138. H. Schägger, “Respiratory chain supercomplexes,” IUBMB Life, vol. 52, no. 3–5, pp. 119–128, 2002. View at Publisher · View at Google Scholar · View at Scopus
  139. H. Schägger and K. Pfeiffer, “Supercomplexes in the respiratory chains of yeast and mammalian mitochondria,” The EMBO Journal, vol. 19, no. 8, pp. 1777–1783, 2000. View at Google Scholar · View at Scopus
  140. Y. Hatefi, “The mitochondrial electron transport and oxidative phosphorylation system,” Annual Review of Biochemistry, vol. 54, pp. 1015–1069, 1985. View at Google Scholar · View at Scopus
  141. S. T. Ohnishi, T. Ohnishi, S. Muranaka et al., “A possible site of superoxide generation in the complex I segment of rat heart mitochondria,” Journal of Bioenergetics and Biomembranes, vol. 37, no. 1, pp. 1–15, 2005. View at Publisher · View at Google Scholar · View at Scopus
  142. S.-W. Cho, J. Lee, and S. Y. Choi, “Two soluble forms of glutamate dehydrogenase isoproteins from bovine brain,” European Journal of Biochemistry, vol. 233, no. 1, pp. 340–346, 1995. View at Google Scholar · View at Scopus
  143. P. J. Shaw, “Molecular and cellular pathways of neurodegeneration in motor neurone disease,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 76, no. 8, pp. 1046–1057, 2005. View at Publisher · View at Google Scholar · View at Scopus
  144. L. Hertz, L. Peng, and G. A. Dienel, “Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 2, pp. 219–249, 2007. View at Publisher · View at Google Scholar · View at Scopus
  145. F. N. Gellerich, Z. Gizatullina, O. Arandarcikaite et al., “Extramitochondrial Ca2+ in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand,” PLoS ONE, vol. 4, no. 12, Article ID e8181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. F. N. Gellerich, Z. Gizatullina, S. Trumbeckaite et al., “The regulation of OXPHOS by extramitochondrial calcium,” Biochimica et Biophysica Acta—Bioenergetics, vol. 1797, no. 6-7, pp. 1018–1027, 2010. View at Publisher · View at Google Scholar · View at Scopus
  147. L. Contreras and J. Satrústegui, “Calcium signaling in brain mitochondria: interplay of Malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways,” The Journal of Biological Chemistry, vol. 284, no. 11, pp. 7091–7099, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. B. Pardo, L. Contreras, A. Serrano et al., “Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria,” The Journal of Biological Chemistry, vol. 281, no. 2, pp. 1039–1047, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. L. Hertz, “Intercellular metabolic compartmentation in the brain: past, present and future,” Neurochemistry International, vol. 45, no. 2-3, pp. 285–296, 2004. View at Publisher · View at Google Scholar · View at Scopus
  150. J. C. K. Lai, J. M. Walsh, S. C. Dennis, and J. B. Clark, “Synaptic and non synaptic mitochondria from rat brain: isolation and characterization,” The Journal of Neurochemistry, vol. 28, no. 3, pp. 625–631, 1977. View at Google Scholar · View at Scopus
  151. A. J. L. Cooper and F. Plum, “Biochemistry and physiology of brain ammonia,” Physiological Reviews, vol. 67, no. 2, pp. 440–519, 1987. View at Google Scholar · View at Scopus
  152. J. G. McCormack and R. M. Denton, “The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex,” Biochemical Journal, vol. 180, no. 3, pp. 533–544, 1979. View at Google Scholar · View at Scopus
  153. A. Panov and A. Scarpa, “Independent modulation of the activity of α-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+,” Biochemistry, vol. 35, no. 2, pp. 427–432, 1996. View at Google Scholar · View at Scopus
  154. R. Balazs, “Control of glutamate metabolism. The effect of pyruvate,” The Journal of Neurochemistry, vol. 12, pp. 63–76, 1965. View at Google Scholar · View at Scopus
  155. R. Balazs, “Control of glutamate oxidation in brain and liver mitochondrial systems,” The Biochemical Journal, vol. 95, pp. 497–508, 1965. View at Google Scholar · View at Scopus
  156. J. Edmond, R. A. Robbins, J. D. Bergstrom, R. A. Cole, and J. De Vellis, “Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture,” Journal of Neuroscience Research, vol. 18, no. 4, pp. 551–561, 1987. View at Google Scholar · View at Scopus
  157. P. Schönfeld, M. R. Wieckowski, M. Lebiedzińska, and L. Wojtczak, “Mitochondrial fatty acid oxidation and oxidative stress: lack of reverse electron transfer-associated production of reactive oxygen species,” Biochimica et Biophysica Acta—Bioenergetics, vol. 1797, no. 6-7, pp. 929–938, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. P. Schonfeld and G. Reiser, “Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain.,” Journal Cerebral Blood Flow Metabolism, vol. 33, pp. 1493–1499, 2013. View at Google Scholar
  159. M. F. Beal, “Energetics in the pathogenesis of neurodegenerative diseases,” Trends in Neurosciences, vol. 23, no. 7, pp. 298–304, 2000. View at Publisher · View at Google Scholar · View at Scopus
  160. M. F. Beal, “Mitochondria take center stage in aging and neurodegeneration,” Annals of Neurology, vol. 58, no. 4, pp. 495–505, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. E. Brouillet, F. Condé, M. F. Beal, and P. Hantraye, “Replicating Huntington's disease phenotype in experimental animals,” Progress in Neurobiology, vol. 59, no. 5, pp. 427–468, 1999. View at Publisher · View at Google Scholar · View at Scopus
  162. M. F. Beal, “Experimental models of Parkinson's disease,” Nature Reviews Neuroscience, vol. 2, no. 5, pp. 325–332, 2001. View at Publisher · View at Google Scholar · View at Scopus
  163. R. Betarbet, T. B. Sherer, G. MacKenzie, M. Garcia-Osuna, A. V. Panov, and J. T. Greenamyre, “Chronic systemic pesticide exposure reproduces features of Parkinson's disease,” Nature Neuroscience, vol. 3, no. 12, pp. 1301–1306, 2000. View at Publisher · View at Google Scholar · View at Scopus
  164. A. Panov, S. Dikalov, N. Shalbuyeva, G. Taylor, T. Sherer, and J. T. Greenamyre, “Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication,” The Journal of Biological Chemistry, vol. 280, no. 51, pp. 42026–42035, 2005. View at Publisher · View at Google Scholar · View at Scopus
  165. A. Panov, S. Dikalov, and S. Dambinova, “Tissue-specific metabolic regulations of respiration and ROS production of the heart, brain and spinal cord mitochondria,” in Proceedings of the FASEB Meeting, Washington, DC, USA, April 2011.
  166. S. Cadenas and M. D. Brand, “Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria,” Biochemical Journal, vol. 348, part 1, pp. 209–213, 2000. View at Publisher · View at Google Scholar · View at Scopus