Brain Cytochrome Oxidase

Functional Significance and Bigenomic Regulation in the CNS
  • Margaret T. T. Wong-Riley
  • Feng Nie
  • Robert F. Hevner
  • Suyan Liu


Cytochrome oxidase is a ubiquitous housekeeping enzyme that holds one of the important keys to life. As a major oxidative enzyme and an energy-generating enzyme, cytochrome oxidase serves as a reliable indicator of neurons’ oxidative capacity and energy metabolism. The tight coupling between energy metabolism and neuronal activity further enables cytochrome oxidase to serve as a sensitive metabolic marker for neuronal functional activity, which includes firing rates of neurons and slow depolarizing potentials occurring primarily in dendrites. In the past two decades, much has been learned about the heterogeneous distribution of cytochrome oxidase in neurons at the regional, laminar, cellular and subcellular levels. The local activity of cytochrome oxidase is correlated with the physiological activity of each area, cell, or subcellular compartment. Regions of high cytochrome oxidase activity are dominated by excitatory, glutamatergic synapses. Changes in the physiological activity of neurons can induce parallel changes in the activity of cytochrome oxidase in developing and adult systems. Cytochrome oxidase activity is controlled mainly by regulation of protein amount, which is regulated transcriptionally. Being bigenomically encoded, cytochrome oxidase is under complex interactive regulation of both mitochondrial and nuclear gene expression. Cytochrome oxidase subunit complementary DNAs were isolated from a murine complementary DNA library, cloned and sequenced. Transcripts from the two genomes have distinct subcellular as well as compartmental distributions suggestive of different regulatory mechanisms. Antibodies generated against subunit proteins from the two genomes also showed differential distributions among neuronal compartments. Nuclear-encoded subunits are translated exclusively in the cell bodies and are delivered intramitochondrially to distal processes. A precursor pool exists in dendrites, where further processing of nuclear-encoded subunits and holoenzyme assembly are presumably governed by local energy demands. Under normal and functionally altered states, cytochrome oxidase activity is linked more closely to transcripts and subunit proteins derived from mitochondrial than from nuclear sources. This indicates that local cytochrome oxidase activity in neurons is controlled mainly by regulation of the mitochondrial genes that encode the catalytic subunits of the enzyme.


Purkinje Cell Cytochrome Oxidase Axon Terminal Lateral Geniculate Nucleus Cytochrome Oxidase Subunit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Attardi, G. and Schatz, G. (1988). Biogenesis of mitochondria. Annu. Rev. Cell Biol., 4, 289–333.PubMedGoogle Scholar
  2. Ausubel F.M., Brent R.. Kingston R.E., Moore D.D., Seidman J.G., Smith J.A. and Struhl K. (1994). Current Pm-locals in Molecular Biology. John Wiley and Sons, New York.Google Scholar
  3. Azzi, A. and Muller. M. (1990). Cytochrome c oxidase: polypeptide composition, role of subunits, and location of active metal centers. Arch. Biochem. Biophys., 280, 242–251.PubMedGoogle Scholar
  4. Bachelard, H.S. Energy utilized by neurotransmitters. In D.H. ingvar and N.A. Lassen (Eds.), Brain Work: The Coupling of Function, Metabolism, and Blood Flow in the Brain, Alfred Benzorr Symposium VIII. Academic Press, New York, 1975, pp. 79–81.Google Scholar
  5. Basu, A. and Avadhani, N.G. (1991). Structural organization of nuclear gene for subunit Vb of mouse mitochondrial cytochrome e oxidase. J. Biol. Chem., 266, 15450–15456.PubMedGoogle Scholar
  6. Bereiter-Hahn, J.. and M. Voth (1983). Metabolic control of shape and structure of mitochondria in situ. Biol. Cell, 47, 309–322.Google Scholar
  7. Bibb, M.J., Van Etten, R.A., Wright, C.T., Walverg, M.W. and Clayton, D.A. (1981). Sequence and gene organization of mouse mitochondrial DNA. Cell, 26, 167–180.PubMedGoogle Scholar
  8. Blass, J.P., Sheu, R.K.-F. and Cedarbaum, J.M. (1988). Energy metabolism in disorders of the nervous system. Rey. Neurol. (Paris), 144, 543–563.Google Scholar
  9. Borowsky, I.W. and Collins, R.C. (1989). Histochemical changes in enzymes of energy metabolism in the dentate gyrus accompany deafferentation and synaptic reorganization. Neurosci., 33, 253–262.Google Scholar
  10. Brown, G.C., Crompton, M. and Wray, S. (1991). Cytochrome oxidase content of rat brain during development. Biochim. Biophys. Acta, 1057, 273–275.PubMedGoogle Scholar
  11. Brown, M.D., Yang, C.-C., Trounce, I., Torroni, A., Lott, M.T. and Wallace, D.C. (1992). A mitochondrial DNA variant, identified in Leber Hereditary Optic Neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit 1. Am. J. Hum. Genet., 51, 378–385.PubMedGoogle Scholar
  12. Capaldi, R.A. (1990). Structure and assembly of cytochrome c oxidase. Arch. Biochem. Biophys., 280, 252–262.PubMedGoogle Scholar
  13. Capaldi R.A., Takamiya S., Zhang Y.Z., Gonzalez-Halphen D. and Yanamura W. (1987). Structure of cytochromes oxidase. Curi: Top. Bioenerg., 15, 91–112.Google Scholar
  14. Carroll, E.W. and Wong-Riley, M.T.T. (1984). Quantitative light and electron microscopic analysis of cytochrome oxidase-rich zones in the striate cortex of the squirrel monkey. J. Comp. Neurol., 222, 1–17.PubMedGoogle Scholar
  15. Cohen, P.J. (1973). Effect of anesthetics on mitochondrial function. Anesthesiology, 39, 153–164.PubMedGoogle Scholar
  16. Cohen, P. Well established systems of enzyme regulation by reversible phosphorylation. in R. Cohen (Ed.) Recently Discovered Systems of Enzyme Regulation by Reversible Phosphorylation. Elsevier/North-Holland Biomedical Press, Amsterdam, 1980a, pp. 1–10.Google Scholar
  17. Cohen, R. Protein phosphorylation and the co-ordinated control of intermediary metabolism. in P. Cohen (Ed.) Recently Discovered Systems of Enzyme Regulation by Reversible Phosphorylation. Elsevier/North-Holland Biomedical Press, Amsterdam, I980b, pp. 255–268.Google Scholar
  18. Collingridge, G.L. and Singer, W. (1990). Excitatory amino acid receptors and synaptic plasticity. Trends Pharm. Sci. 11, 290–296.PubMedGoogle Scholar
  19. Creutzfeldt, O.D. Neurophysiological correlates of different functional states of the brain. In D.H. Ingvar and N.A. Lassen (Eds.), Brain Work. Alfred Benzon Symposium, VIII. Academic Press, New York, 1975, pp. 21–46.Google Scholar
  20. Darriet, D., Der T. and Collins, R.C. (1986). Distribution of cytochrome oxidase in rat brain: studies with diaminobenzidine histochemistry in vitro and [“C]cyanide tissue labeling in vivo. J. Cerebr. Blood Flow Metab., 6, 8–14.Google Scholar
  21. Dawson, T.M. and Snyder, S.H. (1994). Gases as biological messengers: Nitric oxide and carbon monoxide in the brain. J. Neurosci., 14, 5147–5159.PubMedGoogle Scholar
  22. DeYoe, E.A., Trusk, T.C. and Wong-Riley, M.T.T. (1995). Activity correlates of cytochrome oxidase-defined compartments in granular and supragranular layers of primary visual cortex of the macaque monkey. Vis. Neurosci. 12, 629–639.PubMedGoogle Scholar
  23. Dimlich, R.V.W., Showers, M.J. and Shipley, M.T. (1990). Densitometric analysis of cytochrome oxidase in ischemic rat brain. Brain Res., 516, 181–191.PubMedGoogle Scholar
  24. DiRocco, R.J., Kageyama, G.H. and Wong-Riley, M.T.T. (1989). The relationship between CNS metabolism and cytoarchitecture: A review of “C-deoxyglucose studies with correlation to cytochrome oxidase histochemistry. Comput. Med. Imag. and Graph., 13, 81–92.Google Scholar
  25. Erecinska, M., and I.A. Silver (1989). ATP and brain function. J. Cereb. Blood Flow Metab., 9. 2–19.PubMedGoogle Scholar
  26. Ernster, L., Luft, R. and Orrenius, S. (1995). Mitochondria) Diseases. Proceedings of Nobel Symposium 90. Biochim. Biophy. Acta, 1271, 1292.Google Scholar
  27. Errede B., Kamen M. D. and Hatefi Y. (1978). Preparation and properties of complex IV (ferrocytochrome c: oxygen oxidoreductase EC 1.9.3.]). Meth. En_ymol., 53, 40–47.Google Scholar
  28. Evans, M.J. and Scarpulla, R.C. (1990). NRF-l: a trans-activator of nuclear-encoded respiratory genes in animal cells. Genes ampand Dew., 4, 1023–1034.Google Scholar
  29. Fagg, G.E. (1985). L-Glutamate, excitatory amino acid receptors and brain function. Trends Neurosci., 8, 1–4.Google Scholar
  30. Fisher, R.P., Parisi, M.A. and Clayton, D.A. (1989). Flexible recognition of rapidly evolving promoter sequences by mitochondria) transcription factor 1. Genes ampand Dew., 3, 2202–2217.Google Scholar
  31. Fonnum, F. (1984). Glutamate: a neurotransmitter in mammalian brain. J. Newrochem., 42, 1–11.Google Scholar
  32. Forsburg, S.L. and Guarente, L. (1989). Communication between mitochondria and the nucleus in regulation of cytochrome genes in the yeast Saccharomyces cerevisiae. Amtu. Rev. Cell Biol., 5, 153–180.Google Scholar
  33. Garthwaite, J. (1991). Glutamate, nitric oxide and cell-cell signaling in the nervous system. Trends Neurosci., 14, 60–67.PubMedGoogle Scholar
  34. Gonzalez-Lima, F. Brain imaging of auditory learning functions in rats: Studies with fluorodeoxyglucoseautoradiography and cytochrome oxidase histochemistry. In F. Gonzalez-Lima, T. Finkenstadt, and H. Scheich (Eds.), Advances in Metabolic Mapping Techniques Ji r Brain Imaging of Behavioral and Learning Functions. NATO AS1 Series D. Vol. 68, Kluwer Academic Publishers, Dordrecht/Boston/London, 1992, pp. 39–109.Google Scholar
  35. Gonzalez-Lima, F. and Garrosa, M. (1991). Quantitative histochemistry of cytochrome oxidase in rat brain. Neuro-sci. Lett., 123, 251–253.Google Scholar
  36. Goto, Y., Naoki, A. and Taro, O. (1989). Nucleotide sequence of cDNA for rat brain and liver cytochrome c oxidase subunit IV. Nucleic Acids Res., 17, 2851.PubMedGoogle Scholar
  37. Grafstein, B. and Forman, D.S. (1980). Intracellular transport in neurons. Physiol. Rev., 60, 1167–1283.PubMedGoogle Scholar
  38. Gross, N.J., Getz, G.S. and Rabinowitz, M. (1969). Apparent turnover of mitochondrial deoxyribonucleic acid and mitochondria) phospholipids in the tissues of the rat. J. Biol. Chem., 244, 1552–1562.PubMedGoogle Scholar
  39. Grossman L.I., Rosenthal N.H., Akamatsu M. and Erickson R.P. (1995). Cloning, sequence analysis, and expression of a mouse cDNA encoding cytochrome c oxidase subunit VIa liver isoform. Biochim. Biophvs. Acta, 1260, 361–364.Google Scholar
  40. Harding, A.E. (1991). Neurological disease and mitochondrial genes. Trends Neurosci., 14, 132–138.PubMedGoogle Scholar
  41. Hartl, F.U., Pfanner, N., Nicholson, D.W. and Neupert, W. (1989). Mitochondria] protein import. Biochim. Biophys. Acta, 988, 1–45.PubMedGoogle Scholar
  42. Hatefi, Y. (1985). The mitochondrial electron transport and oxidative phosphorylation system. Anno. Rev. Biochem., 54, 1015–1069.Google Scholar
  43. Hevner, R.F. and Wong-Riley, M.T.T. (1989). Brain cytochrome oxidase: Purification, antibody generation, and immunohistochemical/histochemical correlations in the CNS. J. Neurosci., 9, 3884–3898.PubMedGoogle Scholar
  44. Hevner, R.F. and Wong-Riley, M.T.T. (1990). Regulation of cytochrome oxidase protein levels by functional activity in the macaque monkey visual system. J. Neurosci., 10, 1331–1340.PubMedGoogle Scholar
  45. Hevner, R.F. and Wong-Riley, M.T.T. (1991). Neuronal expression of nuclear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: Comparison with CO activity and protein. J. Neurosci., 11, 1942–1958.Google Scholar
  46. Hevner, R.F. and Wong-Riley, M.T.T. (1993). Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons. J. Neurosci., 13, 1805–1819.PubMedGoogle Scholar
  47. Hevner, R.F., Duff, R.S. and Wong-Riley, M.T.T. (1992). Coordination of ATP production and consumption in brain: Parallel regulation of cytochrome oxidase and Na’,K’-ATPase. Neurosci. Lett., 138, 188–192.PubMedGoogle Scholar
  48. Hevner, R.F., Liu, S. and Wong-Riley, M.T.T. (1993). An optimized method for determining cytochrome oxidase activity in brain tissue homogenates. J. Neurosci. Meth., 50, 309–319.Google Scholar
  49. Hevner, R.F., Liu, S. and Wong-Riley, M.T.T. (1995). A metabolic map of cytochrome oxidase in the rat brain: Histochemical, densitometric and biochemical studies. Neurosci., 65, 313–342.Google Scholar
  50. Hicks, T.P., Lodge, D. and McLennan, H. (1987). Excitatory Amino Acid Transmission. Alan R. Liss, New York. Hood, D.A. (1990). Co-ordinate expression of cytochrome c oxidase subunit III and Vic mRNAs in rat tissues. Biochem. J., 269, 503–506.Google Scholar
  51. Hundt, E., Trapp, M. and Kadenbach, B. (1980). Biosynthesis of cytochrome c oxidase in isolated rat hepatocytes. FEBS Lett., 115, 95–99.PubMedGoogle Scholar
  52. Hyde, G.E. and Durham, D. (1990). Cytochrome oxidase response to cochlea removal in chicken auditory brain-stem neurons. J. Comp. Neurol., 297, 329–339.PubMedGoogle Scholar
  53. Ignacio, P.C., Baldwin, B.A., Vijayan, V.K., Tait, R.C. and Gorin, F.A. (1990). Brain isozyme of glycogen phosphorylase: Immunohistological localization within the central nervous system. Brain Res., 529, 42–49.PubMedGoogle Scholar
  54. Isashiki, Y., Nakagawa, M. and Higuchi, I. (1991). Immunohistochemistry of the monkey retina with a monoclonal antibody against subunit V of cytochrome c oxidase. ACTA Ophthal., 69, 321–326.PubMedGoogle Scholar
  55. Jaussi, R., Sonderegger, P., Fluckiger, J. and Christen, P. (1982). Biosynthesis and topogenesis of aspartate aminotransferase isoenzymes in chicken embryo fibroblasts. The precursor of the mitochondrial isoenzyme is either imported into mitochondria or degraded in the cytosol. J. Biol. Chem., 257, 13334–13340.PubMedGoogle Scholar
  56. Jeffrey, P.L., James, K.A.C., Kidman, A.D., Richards, A.M. and Austin, L. (1972). The flow of mitochondria in chicken sciatic nerve. J. Neurobiol., 3, 199–208.PubMedGoogle Scholar
  57. Kadenbach B. and Merle P. (1981). On the function of multiple subunits of cytochrome c oxidase from higher eukaryotes. FEBS Lett., 135, 1-I I.Google Scholar
  58. Kadenbach B., Hartmann R., Glanville R. and Buse G. (1982). Tissue-specific genes code for polypeptide Vla of bovine liver and heart cytochrome c oxidase. FEBS Lett., 138, 236–238.PubMedGoogle Scholar
  59. Kadenbach, B., Jaraush, S., Hartmann, R. and Merle, P. (1983). Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoresis procedure. Anal. Biochem., 129, 517–521.PubMedGoogle Scholar
  60. Kageyama, G.H. and Wong-Riley, M.T.T. (1982). Histochemical localization of cytochrome oxidase in the hippocampus: Correlation with specific neuronal types and afferent pathways. Neurosci., 7, 2337–2361.Google Scholar
  61. Kageyama, G.H. and Wong-Riley, M.T.T. (1984). The histochemical localization of cytochrome oxidase in the retina and lateral geniculate nucleus of the ferret, cat, and monkey, with particular reference to retinal mosaics and ON/OFF-center visual channels. J. Neurosci., 4, 2445–2459.PubMedGoogle Scholar
  62. Kageyama, G.H. and Wong-Riley, M.T.T. (1985). An analysis of the cellular localization of cytochrome oxidase in the lateral geniculate nucleus of the adult cat. J. Comp. Neurol., 242, 338–357.PubMedGoogle Scholar
  63. Kaput, J., Goltz, S. and Blobel, G. (1982). Nucleotide sequence of the yeast nuclear gene for cytochrome c peroxidase precursor. J. Biol. Chem., 257, 15054–15058.PubMedGoogle Scholar
  64. Katz, L.C., Gilbert, C.D. and Wiesel, T.N. (1989). Local circuits and ocular dominance columns in monkey striate cortex. J. Neurosci., 9, 1389–1399.PubMedGoogle Scholar
  65. Krnjevic, K. Coupling of neuronal metabolism and electrical activity. In D.H. Ingvar and N.A. Lassen (Eds.), Brain Work: The Coupling of Function, Metabolism, and Blood Flow in the Brain, Alfred Benzon Symposium VIII. Academic Press, New York, 1975, pp. 65–78.Google Scholar
  66. Krnjevic, K. Neurotransmitters in cerebral cortex: a general account, In E.G. Jones and A. Peter (Eds.), Cerebral Cortex, Vol. 2. Functional Properties of Cortical Cells. Plenum Press, New York, 1984, pp. 39–61.Google Scholar
  67. Krnjevic, K. and S. Schwartz (1966). The action of gamma-aminobutyric acid on cortical neurons. Exp. Brain Res., 3, 320–336.Google Scholar
  68. LaManna, J.C., Kutina-Nelson, K.L., Hritz, M.A., Huang, Z. and Wong-Riley, M.T.T. (1996). Decreased rat brain cytochrome oxidase activity after prolonged hypoxia. Brain Res., 720, 1–6.PubMedGoogle Scholar
  69. Land, P.W. and Simons, D.J. (1985). Metabolic activity in Sml cortical barrels of adult rats is dependent on patterned sensory stimulation of the mystacial vibrissae. Brain Res., 341, 189–194.PubMedGoogle Scholar
  70. Livingstone, M.S., and Hubel, D.H. (1984). Anatomy and physiology of a color system in the primate visual cortex. J. Neurosci., 4, 309–356.PubMedGoogle Scholar
  71. Liu, S., Wilcox, D.A., Sieber-Blum, M. and Wong-Riley, M. (1990). Developing neural crest cells in culture: Correlation of cytochrome oxidase activity with SSEA-I and dopamine beta-hydroxylase immunoreactivity. Brain Res., 535, 271–280.PubMedGoogle Scholar
  72. Liu, S. and Wong-Riley, M.T.T. (1994). Nuclear-encoded mitochondrial precursor protein: Intramitochondrial delivery to dendrites and axon terminals of neurons and regulation by neuronal activity. J. Neurosci., 14, 5338–5351.PubMedGoogle Scholar
  73. Lomax M.I. and Grossman L.I. (1989). Tissue-specific genes for respiratory proteins. Trends Biochem. Sci., 14, 501–503.PubMedGoogle Scholar
  74. Lorenz, T. and Willard, M. (1978). Subcellular fractionation of intra-axonally transported polypeptides in the rabbit visual system. Proc. Natl. Acad. Sci. USA, 75, 505–509.Google Scholar
  75. Lowry, O.H. Energy metabolism in brain and its control. In D.H. Ingvar and N.A. Lassen (Eds.), Brain Work: The Coupling of Function, Metabolism, and Blood Flow in the Brain, Alfred Benzon Symposium VIII. Academic Press, New York, 1975, pp. 48–64.Google Scholar
  76. Luo, X.G., Hevner, R.F. and Wong-Riley, M.T.T. (1989). Double labeling of cytochrome oxidase and gamma aminobutyric acid in central nervous system neurons of adult cats. J. Neurosci. Meth., 30. 189–195.Google Scholar
  77. Maccecchini M.L., Rudin Y, Blobel G. and Schatz G. (1979). Import of proteins into mitochondria: precursor forms of the extramitochondrially made F 1-ATPase subunits in yeast. Proc. Natl. Acad. Sci. USA, 76, 343–347.PubMedGoogle Scholar
  78. Malenka, R.C. and Nicoll, R.A. (1993). NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci., 16, 521–527.PubMedGoogle Scholar
  79. Mata, M., D.J. Fink, H. Gainer, C.B. Smith, L. Davidsen, H. Savaki, W.J. Schwartz, and L. Sokoloff(1980). Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. J. Neurochem., 34, 213–215.Google Scholar
  80. Mawe, G.M., and M.D. Gershon (1986). Functional heterogeneity in the myenteric plexus: Demonstration using cytochrome oxidase as a verified cytochemical probe of the activity of individual enteric neurons../. Comp. Neurol., 249, 381–391.Google Scholar
  81. Mita, S., Schmidt, B., Schon, E.A., DiMauro, S. and Bonilla, E. (1989). Detection of “deleted” mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of a patient with Kearns-Sayre syndrome. Proc. Nail. Acad. Sci. USA, 86, 9509–9513.Google Scholar
  82. Mjaatvedt, A.E. and Wong-Riley M.T.T. (1986). Double-labeling of rat a-motoneurons for cytochrome oxidase and retrogradely transported [’H]WGA. Brain Res., 368, 178–182.PubMedGoogle Scholar
  83. Mjaatvedt, A.E. and Wong-Riley M.T.T. (1988). Relationship between synaptogenesis and cytochrome oxidase activity in Purkinje cells of the developing rat cerebellum. J. Comp. Neurol., 277, 155–182.PubMedGoogle Scholar
  84. Mjaatvedt, A.E. and Wong-Riley, M.T.T. (1991). Effects of unilateral climbing fiber deafferentation on cytochrome oxidase activity in the developing rat cerebellum.. 1. Newt’ evtol., 20, 2–16.Google Scholar
  85. Morgan-Hughes, J.A. (1986). Mitochondrial diseases. Trends Neurosci., 9, 15–19.Google Scholar
  86. Mori, M., Morita, T., Ikeda, F., Amaya, Y., Tatibana, M. and Cohen, P.P. (1981). Synthesis. intracellular transport, and processing of the precursors for mitochondrial ornithine transcarbamylase and carbamoylphosphate synthetase I in isolated hepatocytes. Proc. Natl. Acad. Sci. USA, 78, 6056–6060.PubMedGoogle Scholar
  87. Morris, R.L. and Hollenbeck, P.J. (1993). The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth. J Cell Sci., 104, 917–927.PubMedGoogle Scholar
  88. Munaro, M., Tiranti, V., Sandona, D., Lamantea, E., Uziel, G., Bisson, R. and Zeviani, M. (1997). A single cell complementation class is common to several cases of cytochrome c oxidase-defective Leigh’s syndrome. Hum. Mol. Genet., 6, 221–228.PubMedGoogle Scholar
  89. Nakanishi, S. (1992). Molecular diversity of glutamate receptors and implications for brain function. Science, 258, 597–603.PubMedGoogle Scholar
  90. Nie, F. and Wong-Riley, M.T.T. (1995). Double labeling of GABA and cytochrome oxidase in the macaque visual cortex: Quantitative EM analysis. J. Comp. Neurol., 356, 115–131.PubMedGoogle Scholar
  91. Nie, F. and Wong-Riley, M.T.T. (1996a). Differential glutamatergic innervation in cytochrome oxidase-rich and–poor regions of the macaque striate cortex: Quantitative EM analysis of neurons and neuropil. J. Comp. Neurol., 369, 571–590.PubMedGoogle Scholar
  92. Nie, F. and Wong-Riley, M.T.T. (1996b). Metabolic and neurochemical plasticity of g-aminobutyric acid-immunoreactive neurons in the adult macaque striate cortex following monocular impulse blockade: Quantitative electron microscopic analysis. J. Comp. Neural., 370, 350–366.Google Scholar
  93. Nie, F. and Wong-Riley, M. (1996c). Mitochondrial-and nuclear-encoded subunits of cytochrome oxidase in neurons: Differences in compartmental distribution, correlation with enzyme activity, and regulation by neuronal activity. J. Comp. Neurol., 373, 139–155.PubMedGoogle Scholar
  94. Nobrega, J.N., Raymond, R., DiStefano, L. and Burnham, W.M. (1993). Long-term changes in regional brain cytochrome oxidase activity induced by electroconvulsive treatment in rats. Brain Res., 605, 1–8.PubMedGoogle Scholar
  95. Palay, S.L. and Chan-Palay, V. (1974). Cerebellar Cortex. Springer, New York.Google Scholar
  96. Parisi, M.A., Xu, B. and Clayton, D.A. (1993). A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro. Mol. Cell. Biol., 13, 1951–1961.PubMedGoogle Scholar
  97. Pfeiffer, B., Elmer, K., Roggendorf, W., Reinhart, P.H., and Hamprecht, B. (1990). Immunohistochemical demonstration of glycogen phosphorylase in rat brain slices. Histochem., 94, 73–80.Google Scholar
  98. Poyton R.O., Trueblood C.E., Wright R.M. and Farrell L.E. (1988). Expression and function of cytochrome c oxidase subunit isologues. Ann. N.Y. Acad. Sci., 550, 289–307.PubMedGoogle Scholar
  99. Reid, G.A., Yonetani, T. and Schatz, G. (1982). Import of proteins into mitochondria: import and maturation of the mitochondria) intermembrane space enzymes cytochrome b, and cytochrome c peroxidase in intact yeast cells. J. Biol. Chem., 257, 13068–13074.PubMedGoogle Scholar
  100. Reimann, A., Huther, F.-J., Berden, J.A. and Kadenbach, B. (1988). Anions induce conformational changes and influence the activity and photoaffinity-labeling by 8-azido-ATP of isolated cytochrome c oxidase. Biochem. J., 254, 723–730.PubMedGoogle Scholar
  101. Rosevear, P., VanAken, T., Baxter, J. and Ferguson-Miller, S. (1980). Alkyl glycoside detergents: a simpler synthesis and their effects on kinetic and physical properties of cytochrome c oxidase. Biochem., 19, 4108–4115.Google Scholar
  102. Ruscak, M., and Whittam, R. (1967). The metabolic response of brain slices to agents affecting the sodium pump. J. Physiol., 19, 595–610.Google Scholar
  103. Sambrook J., Fritsch E.F. and Maniatis T. (1989). Molecular cloning: a laboratory manual, 2d ed. Cold Spring Harbor Press, Cold Spring Harbor, New York.Google Scholar
  104. Sanger F., Nicklen S. and Coulson A.R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA, 74, 5463–5467.PubMedGoogle Scholar
  105. Scarpul la, R.C. (1997). Nuclear control of respiratory chain expression in mammalian cells. J. Bioenerg. Biomemb., 29, 109–119.Google Scholar
  106. Schimke, R.T. and Doyle, D. (1970). Control of enzyme levels in animal tissues. Annu. Rev. Biochem., 39, 929–976.PubMedGoogle Scholar
  107. Schlerf A., Droste M., Winter M. and Kadenbach B. (1988). Characterization of two different genes (cDNA) for cytochrome c oxidase subunit Vla from heart and liver of the rat. EMBOJ., 7, 2387–2391.Google Scholar
  108. Schwartz, W.J. and Sharp, F.R. (1978) Autoradiographic maps of regional brain glucose consumption in resting, awake rats using [“C]2-deoxyglucose. J. Comp. Neurol., 177, 335–360.PubMedGoogle Scholar
  109. Schwartz, W.J., C.B. Smith, L. Davidsen, H. Savaki, L. Sokiloff, M. Mata, D.J. Fink, and H. Gainer (1979). Metabolic mapping of functional activity in the hypothalamo-neurohypophyseal system of the rat. Science, 205, 723–725.PubMedGoogle Scholar
  110. Schwerzmann, K., Hoppeler, H., Kayar, S.R. and Weibel, E.R. (1989). Oxidative capacity of muscle and mitochondria: Correlation of physiological, biochemical, and morphometric characteristics. Proc. Natl. Acad. Sci. USA, 86, 1583–1587.PubMedGoogle Scholar
  111. Siegel, G., Agranoff, B., Albers, R.W. and Molinoff, P. (1989). Basic Neurochemistry. 4th ed. Raven Press, New York.Google Scholar
  112. Smith, L. and Camerino, P.W. (1963). The reaction of particle-bound cytochrome c oxidase with endogenous and exogenous cytochrome c. Biochem., 2, 1432–1439.Google Scholar
  113. Sokoloff, L. Changes in enzyme activities in neural tissues with maturation and development of the nervous system. In F.O. Schmitt and F.G. Worden (Eds.), The Neurosciences: Third Study Program. MIT Press, Cambridge, 1974, pp. 885–898.Google Scholar
  114. Sokoloff, L. (1981). Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J. Cereb. Blood Flow Metab., 1, 7–36.PubMedGoogle Scholar
  115. Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M.H., Patlak, C.S., Pettigrew, K.D., Sakurada. O. and Shinohara, M. (1977). The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem., 28, 897–916.Google Scholar
  116. Suske, G., Enders, C., Schierl’, A. and Kadenbach, B. (1988). Organization and nucleotide sequence of two chromosomal genes for rat cytochrome c oxidase subunit Vic: a structural and a processed gene. DNA, 7, 163–171.PubMedGoogle Scholar
  117. Taanman J.-W., Turina P. and Capaldi R.A. (1994). Regulation of cytochrome c oxidase by interaction of ATP at two binding sites, one on subunit VIa. Biochem., 33, 11833–11841.Google Scholar
  118. Thompson, C.C., Brown, T.A. and McKnight, S.L. (1991). Convergence of Ets-and notch-related structural motifs in a heteromeric DNA binding complex. Science, 253, 762–768.PubMedGoogle Scholar
  119. Trembleau A., Morales M. and Bloom F.E. (1994). Aggregation of vasopressin mRNA in a subset of axonal swellings of the median eminence and posterior pituitary: Light and electron microscopic evidence. J. Neuro-sci., 14, 39–53.Google Scholar
  120. Vale, R.D., Schnapp, B.J., Reese, T.S. and Sheetz, M.P. (1985). Movement of organelles along filaments dissociated from the axoplasm of the squid giant axon. Cell, 40, 449–454.PubMedGoogle Scholar
  121. Vanneste, W.H., Ysebaert-Vanneste, M. and Mason, H.S. (1974). The decline of molecular activity of cytochrome oxidase during purification. J. Biol. Chem., 249, 7390–7401.PubMedGoogle Scholar
  122. Viebrock, A., Perz, A. and Sebald, W. (1982). The imported preprotein of the proteolipid subunit of the mitochondrial ATP synthase from Neurospora crassa. Molecular cloning and sequencing of the mRNA. EMBO J., 1, 565–571.PubMedGoogle Scholar
  123. Vik, S.B. and Capaldi, R. (1980). Conditions for optimal electron transfer activity of cytochrome c oxidase isolated from beef heart mitochondria. Biochem. Biophys. Res. Comm., 94. 348–354.PubMedGoogle Scholar
  124. Virbasius, J.V. and Scarpulla, R.C. (1990). The rat cytochrome c oxidase subunit IV gene family: tissue-specific and hormonal differences in subunit IV and cytochrome c mRNA expression. Nucleic Acids Res., 18, 6581–6586.PubMedGoogle Scholar
  125. Virbasius, J.V. and Scarpulla, R.C. (1994). Activation of the human mitochondria] transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc. Natl. Acad. Sci. USA, 91, 1309–1313.PubMedGoogle Scholar
  126. Virbasius, J.V., Virbasius, C.A. and Scarpulla, R.C. (1993). Identity of GABP with NU-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Genes Dev., 7, 380–392.PubMedGoogle Scholar
  127. Wallace, D.C. (1992). Diseases of the mitochondria] DNA. Annu. Rev. Biochem., 61, 1175–1212.PubMedGoogle Scholar
  128. Wallace, D.C. (1995). 1994 William Allan Award Address: Mitochondria) DNA variation in human evolution, degenerative disease, and aging. Am. J. Hum. Genet., 57, 201–223.Google Scholar
  129. Warren, R., Tremblay, N. and Dykes, R.W. (1989). Quantitative study of glutamic acid decarboxylase-immunoreactive neurons and cytochrome oxidase activity in normal and partially deafferented rat hindlimb somatosensory cortex. J. Comp. Neurol., 288, 583–592.PubMedGoogle Scholar
  130. Wharton D. C. and Tzagoloff A. (1967). Cytochrome oxidase from beef heart mitochondria. Meth. Enzymol., 10. 245–250Google Scholar
  131. Wikstrom M., Krab K. and Saraste M. (1981). Cytochrome Oxidase. A synthesis. Academic Press, New York.Google Scholar
  132. Williams, R.S. (1986). Mitochondrial gene expression in mammalian striated muscle: evidence that variation in gene dosage is the major regulatory event. J. Biol. Chem., 261, 12390–12394.PubMedGoogle Scholar
  133. Williams, R.S. and Harlan, W. (1987). Effects of inhibition of mitochondrial protein synthesis in skeletal muscle. Am. J. Physiol., 253, C866–871.PubMedGoogle Scholar
  134. Williams, R.S., Salmons, S., Newsholme, E.A., Kaufman, R.E. and Mellor, J. (1986). Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle. J. Biol. Chem., 261, 376–380.PubMedGoogle Scholar
  135. Williams, R.S., Garcia-Moll, M., Mellor, J., Salmons, S. and Harlan, W. (1987). Adaptation of skeletal muscle to increased contractile activity: expression of nuclear genes encoding mitochondria) proteins. J. Biol. Chem., 262, 2764–2767.PubMedGoogle Scholar
  136. Wong-Riley, M. (1979). Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res., 171, 11–28.PubMedGoogle Scholar
  137. Wong-Riley, M.T.T. (1989). Cytochrome oxidase: An endogenous metabolic marker for neuronal activity. Trends Neurosci., 12, 94–101.PubMedGoogle Scholar
  138. Wong-Riley, M.T.T. Primate Visual Cortex: Dynamic metabolic organization and plasticity revealed by cytochrome oxidase. In A. Peters and K. Rockland (Eds.), Cerebral Cortex, Vol. l0, Primary Visual Cortex in Primates. Plenum Press, New York, 1994, pp. 141–200.Google Scholar
  139. Wong-Riley, M.T.T. and Carroll, E.W. (1984a) Quantitative light and electron microscopic analysis of cytochrome oxidase-rich zones in V II prestriate cortex of the squirrel monkey. J. Comp. Neural., 222, 18–37.Google Scholar
  140. Wong-Riley, M., and Carroll, E.W. (1984b). The effect of impulse blockage on cytochrome oxidase activity in the monkey visual system. Nature, 307, 262–264.PubMedGoogle Scholar
  141. Wong-Riley, M.T.T. and Kageyama, G.H. (1986). Localization of cytochrome oxidase in the spinal cord and dorsal root ganglia, with quantitative analysis of ventral horn cells in monkeys. J. Comp. Neural., 245, 41–61.Google Scholar
  142. Wong-Riley, M.T.T. and Norton, T.T. (1988). Histochemical localization of cytochrome oxidase activity in the visual system of the tree shrew: Normal patterns and the effect of retinal impulse blockage.. 1. Comp. Neural., 272, 562–578.Google Scholar
  143. Wong-Riley, M., and Riley, D.A. (1983). The effect of impulse blockage on cytochrome oxidase activity in the cat visual system. Brain Res., 261, 185–193.PubMedGoogle Scholar
  144. Wong-Riley, M.T.T. and Welt, C. (1980). Histochemical changes in cytochrome oxidase of cortical barrels following vibrissal removal in neonatal and adult mice. Proc. Natl. Acad. Sci., 77, 2333–2337.PubMedGoogle Scholar
  145. Wong-Riley, M.T.T., Merzenich, M.M. and Leake, P.A. (1978). Changes in endogenous enzymatic reactivity to DAB induced by neuronal inactivity. Brain Re., 141, 185–192.Google Scholar
  146. Wong-Riley, M.T.T., Walsh, S.M., Leake-Jones, P.A., and Merzenich, M.M. (1981). Maintenance of neuronal activity by electrical stimulation of unilaterally deafened cats demonstrable with the cytochrome oxidase technique. Ann. Otol. Rhino). Laryngol. 90, Suppl. 82, 30–32.Google Scholar
  147. Wong-Riley, M.T.T., Tripathi, S.C., Trusk, T.C., and Hoppe, D.A. (1989a). Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex. I. Quantitative EM analysis of neurons. Vis. Neurosci., 2, 483–497.PubMedGoogle Scholar
  148. Wong-Riley, M, Trusk, T.C., Tripathi, S.C. and Hoppe, D.A. (1989b). Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex. II. Quantitative EM analysis of neuropil. Vis. Neurosci., 2, 499–514.PubMedGoogle Scholar
  149. Wong-Riley, M.T.T., Hevner, R.F., Cutlan, R., Earnest, M., Egan, R., Frost, J. and Nguyen, T. (1993). Cytochrome oxidase in the human visual cortex: Distribution in the developing and the adult brain. Vis. Neurosci., 10, 41–58.PubMedGoogle Scholar
  150. Wong-Riley, M.T.T., Trusk, T.C., Kaboord, W., and Huang, Z. (1994). Effect of retinal impulse blockage on cytochrome oxidase-poor interpuffs in the macaque striate cortex: quantitative EM analysis of neurons. J. Neurocvtol.. 23. 533–553.Google Scholar
  151. Wong-Riley, M.T.T., Mullen, M.A., Huang, Z. and Guyer, C. (1997a). Brain cytochrome oxidase subunit complementary DNAs: Isolation, subcloning, sequencing, light and electron microscopic in situ hybridization of transcripts, and regulation by neuronal activity. Neurosci., 76, 1035–1055.Google Scholar
  152. Wong-Riley, M., Antuono, P., Ho, K.-C., Egan, R., Hevner, R., Liebl, W., Huang, Z., Rachel, R. and Jones, J. (1997b). Cytochrome oxidase in Alzheimer’s Disease: Biochemical, histochemical, and immunohistochemical analyses of the visual and other systems. Vision Research,Special issue on Alzheimer’s Disease and the Visual System, in press.Google Scholar
  153. Wong-Riley, M., Anderson, B., Liebl, W. and Huang, Z. (1998a). Neurochemical organization of the macaque striate cortex: Correlation of cytochrome oxidase with Na*K*ATPase, NADPH-diaphorase, nitric oxide synthase, and NMDA receptor subunit I. Neurosci.,in press.Google Scholar
  154. Wong-Riley, M.T.T., Huang, Z., Liebl, W., Nie, F., Xu, H. and Zhang, C. (1998b). Neurochemical organization of the macaque retina: Effect of TTX on levels and gene expression of cytochrome oxidase and nitric oxide synthase, and on the immunoreactivity of Na’K`ATPase and NMDA receptor subunit 1. Vis. Res.,in press.Google Scholar
  155. Woodford, B.J. and Blanks, J.C. (1989). Uptake of tritiated thymidine in mitochondria of the retina. Invest. Ophthabnol. Vis. Sci., 30, 2528–2532.Google Scholar
  156. Woodward, D.J., Hoffer, B.J., Siggins, G.R. and Bloom, F.E. (1971) The ontogenetic development of synaptic junctions, synaptic activation and responsiveness to neurotransmitter substances in rat cerebellar Purkinje cells. Brain Res., 34, 73–79.PubMedGoogle Scholar
  157. Yamada, M., Amuro, N., Goto, Y. and Okazaki, T. (1990). Structural organization of the rat cytochrome e oxidase subunit IV gene. J. Biol. Chem., 265, 7687–7692.PubMedGoogle Scholar
  158. Yip, V.S.. Zhang, W.-P., Woolsey, T.A. and Lowry, O.H. (1987). Quantitative histochemical and microchemical changes in the adult mouse central nervous system after section of the infraorbital and optic nerves. Brain Res., 406, 157–170.PubMedGoogle Scholar
  159. Zhang, C. and Wong-Riley, M.T.T. (1996). Do nitric oxide synthase, NMDA receptor subunit RI and cytochrome oxidase co-localize in the rat central nervous system? Brain Res., 729, 205–215.PubMedGoogle Scholar
  160. Zhang, C. and Wong-Riley, M.T.T. (1997). Effect of depolarization on cytochrome oxidase gene expression in primary neuronal culture of rat cortex. Soc. Neurosci. Ahstr., 23, 89.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Margaret T. T. Wong-Riley
    • 1
  • Feng Nie
    • 1
  • Robert F. Hevner
    • 1
  • Suyan Liu
    • 1
  1. 1.Department of Cellular Biology and AnatomyMedical College of WisconsinMilwaukeeUSA

Personalised recommendations