Molecular Mechanisms of Impaired Mitochondrial Gene Expression in Alzheimer’s Disease

  • Krish Chandrasekaran
  • Kimmo Hatanpää
  • Li-Ing Liu
  • Stanley I. Rapoport


In vivo positron emission tomography imaging suggests that brain energy metabolism is reduced in patients with Alzheimer’s disease. In vitro studies using postmortem brains from Alzheimer’s disease patients show corresponding decreases in expression of mitochondrial genes encoding for enzymes of oxidative energy metabolism. Neurodegeneration and age-dependent deletions and mutations in mitochondrial DNA are among factors that have been proposed to be responsible for this reduction. Recent findings, however, suggest that reduced energy metabolism in Alzheimer’s disease is coupled to reduced neuronal activity. It is proposed that in Alzheimer’s disease, reduced synaptic input and downregulation of oxidative energy metabolism render neurons more vulnerable to sudden energy metabolic insults such as excitotoxicity and thereby hasten neuro-degeneration.


Cytochrome Oxidase Neurofibrillary Tangle Neuritic Plaque Subunit mRNA Nuclear Respiratory Factor 
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  1. 1.
    Abe, K., Kawagoe, J., and Kogure, K. (1993) Early disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia, Neurosci Lett., 153, 173–176.PubMedCrossRefGoogle Scholar
  2. 3.
    Ames, B.N., Shigenaga, M.K., and Hagen, T.M. (1995). Mitochondrial decay in aging. Biochim. Biophvs. Acta., 1271, 165–170.CrossRefGoogle Scholar
  3. 4.
    Anderson, S., Bankier, A.T., Barrell, B.G., de Bruijn, M.H.L., Coulson, A.R., Drouin, J., Eperon, I.C., Nierlich, D.P., Roe, B.A., Sanger, F., Schreier, P.H., Smith, A.J.H., Staden, R. and Young, I.G. (1981) Sequence and organization of the human mitochondrial genome, Nature, 290, 457–465.PubMedCrossRefGoogle Scholar
  4. 5.
    Attardi, G., Chomyn, A., King, M.P., Kruse, B., Polosa, P.L., and Murdter, N.N. (1989). Biogenesis and assembly of the mitochondria] respiratory chain: Structural, genetic and pathological aspects. Biochem. Soc. Trans., 18, 509–513.Google Scholar
  5. 6.
    Attardi, G., and Schatz, G. (1988). Biogenesis of mitochondria. Annu. Rev. Cell Biol., 4, 289–333.PubMedCrossRefGoogle Scholar
  6. 7.
    Beal, M.F., Hyman, B.T. and Koroshetz, W. (1993). Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends. Neurosci., 16, 125–131.PubMedCrossRefGoogle Scholar
  7. 8.
    Blass, J.P., and Gibson, G.E. (1991). The role of oxidative abnormalities in the pathophysiology of Alzheimer’s disease. Rev. Neurol. (Paris)., 147, 513–525.Google Scholar
  8. 9.
    Bodenteich, A., Mitchell, L.G. and Merril, C.R. (1991). A lifetime of retinal light exposure does not appear to increase mitochondrial mutations. Gene, 108. 305–310.PubMedCrossRefGoogle Scholar
  9. 10.
    Capaldi, R.A. (1990) Structure and function of cytochrome c oxidase, Anna. Rev. Biochem., 59, 569–596.CrossRefGoogle Scholar
  10. 11.
    Chandrasekaran, K., Stoll, J., Giordano, T., Atack, J.R., Matocha, M.F., Brady, D.R. and Rapoport, S.I. (1992) Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain, J. Neurosci. Res., 32, 415–423.PubMedCrossRefGoogle Scholar
  11. 12.
    Chandrasekaran, K., Stoll, J., Brady, D.R., and Rapoport, S.I. (1992). Localization of cytochrome oxidase (COX) activity and cox mRNA in the hippocampus and entorhinal cortex in the monkey brain: Correlation with specific neuronal pathways. Bruin Res., 579, 333–336.CrossRefGoogle Scholar
  12. 13.
    Chandrasekaran, K., Stoll, J., Rapoport, S.I., and Brady, D.R. (1993). Localization of cytochrome oxidase (COX) activity and COX mRNA in the perirhinal and superior temporal sulci of the monkey brain. Brain Research., 606, 213–219.PubMedCrossRefGoogle Scholar
  13. 14.
    Chandrasekaran, K., Giordano, T., Brady. D.R., Stoll, J., Hatanpää, K., Martin, L.J., and Rapoport, S.l. (1994). Impairment in gene expression of oxidative metabolism in vulnerable brain regions in Alzheimer’s disease. Neurobiol. Aging., 15: S125.Google Scholar
  14. 15.
    Chandrasekaran, K., Giordano,T., Brady, D.R., Stoll, J., Martin, L.J., and Rapoport, S.I. (1994). Impairment of mitochondrial cytochrome oxidase gene expression in Alzheimer’s disease. Mol. Brain Res., 24: 336–340.PubMedCrossRefGoogle Scholar
  15. 16.
    Chandrasekaran, K., Hatanpää, K., Brady, D.R. and Rapoport, S.I. (1996) Evidence for physiological downregulation of brain oxidative phosphorylation in Alzheimer’s disease, Exp. Neurol., 142, 80–88.PubMedCrossRefGoogle Scholar
  16. 17.
    Chandrasekaran, K., Hatanpää, K., Rapoport, S.I., and Brady, D.R. (1997) Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex of Alzheimer’s disease. Mol. Brain Res., 44, 99–104.PubMedCrossRefGoogle Scholar
  17. 18.
    Chandrasekaran, K., Li-Ing, L., Hatanpää, K. and Rapoport, S.I. (1997). Regulation of mitochondrial DNA-encoded cytochrome oxidase subunit gene expression in PC12 cells. Soc. Neurosci. Abstr., 23, 1639.Google Scholar
  18. 19.
    Corral-Debrinski, M., Horton, T., Lott, M.T., Shoefner, J.M., Mcee, A.C., Beal, M.F., Garham. B.H., and Wallace, D.C. (1994). Marked changes in mitochondrial DNA deletion levels in Alzheimer’s brains. Genomics, 23, 471–476.PubMedCrossRefGoogle Scholar
  19. 20.
    Corral-Debrinski, M., Stepien, G., Shoefner, J.M., Lott, M.T. Kanter, K., Wallace, D.C. (1991). Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease. J. Am. Med. Assoc., 266, 1812–1816.CrossRefGoogle Scholar
  20. 21.
    Davies, C.A., Mann, D.M.A., Sumpter, P.O., and Yates, P.O. (1987). A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. J. Neural. Sci., 78, 151–164.CrossRefGoogle Scholar
  21. 22.
    Davis, R.E., Miller, J.S., Herrnstadt, C., Ghosh, S.S., Fatly, E., Shinobu, L.A., Galasko, D., Thal, L.J., Beal, M.F., Howell, N. And Parker Jr, W.D. (1997) Mutations in mitochondria) cytochrome e oxidase genes segregate with late-onset Alzheimer’s disease, Proc. Natl. Acad. Sci. USA, 94,4526–4531.PubMedCrossRefGoogle Scholar
  22. 23.
    Decarli, C.S., Atack, J.R., Ball, M.J., Kaye, J.A., Grady, C.L., Fewster, P., Pettigrew, K.D., Rapoport, S.I., and Schapiro, M.B. (1992). Post-mortem regional neurofibrillary tangle densities but not senile plaque densities are related to regional cerebral metabolic rates for glucose during life in Alzheimer’s disease patients. Neurodegeneration., I, 113–121.Google Scholar
  23. 24.
    DeKoky, S.T., and Scheff, S.W. (1990). Synapse loss in frontal cortex biopsies in Alzheimer’s disease: Correlation with cognitive severity. Ann. Neurol., 27, 457–464.CrossRefGoogle Scholar
  24. 25.
    Dietrich, W.D., Durham, D., Dietrich, W.D., Durham, D., Lowry, O.H., and Woolsey, T.A. (1982). “Increased” sensory stimulation leads to changes in energy-related enzymes in the brain. J. Neurosci., 2, 1608–1613.PubMedGoogle Scholar
  25. 26.
    Erecinska, M., Silver, I.A. (1989). ATP and brain function. J. Cereb. Blood Flow Metab., 9, 2–19.PubMedCrossRefGoogle Scholar
  26. 27.
    Frackowiak, R.S., Herold, S., Petty, R.K.H. and Morgan-Hughes, J.A. (1988). The cerebral metabolism of glucose and oxygen measured with positron emission tomography in patients with mitochondria) diseases. Brain, 111, 1009–1024.PubMedCrossRefGoogle Scholar
  27. 28.
    Fukuyama, R.F., Hatanpää, K., Rapoport, S.I., and Chandrasekaran, K. (1996). Gene expression of ND4, a subunit of complex of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer’s disease patients. Brain Res., 713, 290–293.PubMedCrossRefGoogle Scholar
  28. 29.
    Gadaleta, M.N., Petruzzella, V., Renis, M., Fracasso, F., and Cantatore, R. (1990). Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Ern: J. Biochem., 187, 501–506.CrossRefGoogle Scholar
  29. 30.
    Gelfand, R., and Attardi, G. (1981). Synthesis and turnover of mitochondria) ribonucleic acid in HeLa cells: The mature ribosomal and messenger ribonucleic acid species are metabolically unstable. Mol. Cell. Biol., 1, 497–511.PubMedGoogle Scholar
  30. 31.
    Gentleman, S.M., Roberts, G.W. (1995) Immunocytochemistry: a neuropathological perspective. Appendix: immunostaining protocol. In Roberts, G.W. and Polak, J.M. (Eds). Molecular neuropathology, Cambridge, England, Cambridge University Press. pp 72.Google Scholar
  31. 32.
    Goto, Y., Nonaka, L, and Horai, S. (1990). A mutation in the tRNA(Leu) (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature, 248, 651–653.CrossRefGoogle Scholar
  32. 33.
    Grady, C.L., Haxby, J.V., Horwitz, B., Gillette, J., Selerno, A., Gonzalez-Aviles, A., Ungerleider, L.E., Carson, R.E., Herscovitch, P., Schapiro, M.B., and Rapoport, S.I. (1993). Activation of cerebral blood flow during a visuoperceptual task in patients with Alzheimer’s-type dementia. Neurobio!. Aging., 14, 35–44.CrossRefGoogle Scholar
  33. 34.
    Greene, J.G. and Greenamyre, J.T. (1996) Bioenergetics and excitotoxicity. Prog. Neurobiol., 48 (6), 613–634.PubMedCrossRefGoogle Scholar
  34. 35.
    Harman, D. (1992). Free radical theory of aging. Mutation. Res., 275, 257–266.PubMedCrossRefGoogle Scholar
  35. 36.
    Harris, M.E., Hensley, K., Butterfield, D.A., Leedle, R.A., and Carney, J.M. (1995). Direct evidence of oxidative injury produced by the Alzheimer’s beta-amyloid peptide (l-40) in cultured hippocampal neurons. Exp. Neurol., 131, 193–202.PubMedCrossRefGoogle Scholar
  36. 37.
    Hatanpää, K., Brady, D.R., Stoll, J., Rapoport, S.I., and Chandrasekaran, K. (1994). Localization of the deficit in cytochrome oxidase (COX) activity and COX subunit mRNA within the cerebral cortex in Alzheimer’s disease. Soc. Neurosci. Abstr, 20, 1253.Google Scholar
  37. 38.
    Hatanpää, K., Brady, D.R., Stoll, J., Rapoport, Si, and Chandrasekaran, K. (1996) Neuronal activity and early neurofibrillary tangles in Alzheimer’s disease. Ann. Neurol., 40, 411–420.PubMedCrossRefGoogle Scholar
  38. 39.
    Hatanpää, K., Brady, D.R., Chandrasekaran, K. and Rapoport, S.I. (1996) Neuronal energy metabolism is not reduced by senile plaques in Alzheimer’s disease. Soc. Neurosci. Absa:, 22, 1 174.Google Scholar
  39. 40.
    Hayakawa, K., Ozawa, T., Sugiyama, M., Tanaka, M., and Ozawa, T. (1991). Massive conversion of guanosine to 8-hydroxyguanosine in mouse liver mitochondrial DNA by administration of azidothymidine. Biochem. Biophys. Res. Commun., 176, 87–93.PubMedCrossRefGoogle Scholar
  40. 41.
    Hayashi, J.1., Ohta, S., Kagawa, Y., Kondo, H., Kaneda, H., Yonekawa, H., Takai, D., and Miyabayashi, S. (1994). Nuclear but not mitochondrial genome involvement in human age-related mitochondrial dysfunction. J. Biol. Chem., 269, 6878–6883.PubMedGoogle Scholar
  41. 42.
    Heddi, A., Lestienne, P., Wallace, D.C., and Stepien, G. (1993). Mitochondria) DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production. J. Biol. Chem., 268, 12156–12163.PubMedGoogle Scholar
  42. 43.
    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.PubMedCrossRefGoogle Scholar
  43. 44.
    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. Neuroscience, 65, 313–342.PubMedCrossRefGoogle Scholar
  44. 45.
    Hevner, R.F., and Wong-Riley, M.T.T. (1991). Neuronal expression of nuelear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: Comparison with CO activity and protein..1. Neurosci. 1 I: 1942–1958.Google Scholar
  45. 46.
    Hcvner, R.F., and Wong-Riley, M.T.T. (1993). Mitochondrial and nuelear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons. J. Neurosci.. 13, 1805–1819.Google Scholar
  46. 47.
    Horton, J.C., and Hubel, D.H. (1981). Regular patchy distribution of cytochrome oxidase staining in primary visual cortex of macaque monkey. Nature, 292, 762–764.PubMedCrossRefGoogle Scholar
  47. 48.
    Hutchin, T., and Cortopassi, G. (1995). A mitochondrial DNA clone is associated with increased risk for Alzheimer’s disease. Proc. Natl. Acad. Sci., 92, 6892–6895.PubMedCrossRefGoogle Scholar
  48. 49.
    Ikebe. S., Tanaka, M., Ohno, K., Sato, W., Hattori, K., Kondo, T., Mizuno, Y., and Ozawa, T. (1990). Increase of deleted mitochondrial DNA in the striatum of Parkinson’s disease and senescence. Biochem. Biophvs. Res. Commtt., 179, 1044–1048.CrossRefGoogle Scholar
  49. 50.
    Kadenbach, B., Kunh-Nentwig, L. and Buge, U.(I 987) Evolution of a regulatory enzyme: cytochrome-coxidase (complex IV), Cu,,: Top. Bioenerg_, 15, 113–161.Google Scholar
  50. 51.
    Kagawa, Y., and Ohta, S. (1990). Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control. lot. J. Biochem., 22: 219–229.Google Scholar
  51. 52.
    Khachaturian, Z.S. (1985) Diagnosis of Alzheimer’s disease. Arch Neurol., 42, 1097–1 105.Google Scholar
  52. 53.
    Kish, S.J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L-J., Wilson, J.M., Distefano, L.M., and Nobrega, J.N. (1992). Brain cytochrome oxidase in Alzheimer’s disease. J Neurochem., 59, 776–779.PubMedCrossRefGoogle Scholar
  53. 54.
    Lewis, D.A., Campbell, M.J., Terry, R.D., and Morrison, J.H. (1987). Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: A quantitative study of visual and auditory cortices. J. Neurosci., 7, 1799–1808.PubMedGoogle Scholar
  54. 55.
    Linnane, A.W., Marzuki, W.S., Ozawa, T., and Tanaka, M. (1989). Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet, 1, 642–645.PubMedCrossRefGoogle Scholar
  55. 56.
    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 of neuronal activity. J. Neurosci., 14, 5338–5351.PubMedGoogle Scholar
  56. 57.
    McGeer, P.L., Kamo, H., Harrop, R., McGeer, E.G., Martin, W.R.W., Pate, B.D., and Li, D.K.B. (1986). Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer’s disease. Neurology. 36, 1569–1574.PubMedCrossRefGoogle Scholar
  57. 58.
    Mecocci, P., MacGarvey, U., and Beal, M.F. (1994). Oxidative damage to mitochondria DNA is increased in Alzheimer’s disease. Ann. Neurol., 36, 747–751.PubMedCrossRefGoogle Scholar
  58. 59.
    Mentis, M.J., Horwitz, B., Grady, C.L., Alexander, G.E., Vanmeter, J.W., Maisog, J.M., Pietrini, P., Schapiro, M.B. and Rapoport, S.I. (1996) Visual cortical dysfunction in Alzheimer’s disease evaluated with a temporally graded “stress test” during PET, Am. J. Psychiatry, 153, 32–40.PubMedGoogle Scholar
  59. 60.
    Mirra, S.S., Hart, M.N. and Terry, R.D. (1993) Making the diagnosis of Alzheimer’s disease. Arch. Pathol. Lab. Med., 117, 132–144.PubMedGoogle Scholar
  60. 61.
    Mutsiya, E.M., Bowling, A.C., and Beal, M.F. (1994). Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J. Neurochen., 63, 2179–2184.CrossRefGoogle Scholar
  61. 62.
    Parker, W.D., Jr, Filley,C.M., and Parks, J.K. (1990). Cytochrome oxidase deficiency in Alzheimer’s disease. Neuaology, 40, 1302–1303.Google Scholar
  62. 63.
    Parker, W.D., Jr, Mahr, N.J., Filley, C.M., Parks, J.K., Hughes, D., Young, D.A., and Cullum, C.M. (1994). Reduced platelet cytochrome c oxidase activity in Alzheimer’s disease. Neurology, 44, 1086–1090.PubMedCrossRefGoogle Scholar
  63. 64.
    Parker, W.D., Jr, Parks, J., Filley, C.M., and Kleinschmidt-Demasters, B.K. (1994). Electron transport chain defects in Alzheimer’s disease brain. Neurology, 44, 1090–1096.PubMedCrossRefGoogle Scholar
  64. 65.
    Pietrini, P., Furey, M.L., Dani, A., Freo, U., Mentis, M.J., Alexander, G.E., and Rapoport, S.1. (1996). Functional response to audiovisual stimulation in Alzheimer’s patients: Potential for therapeutic interventions. Abstr Soc. Neurosci., 22, 1176.Google Scholar
  65. 66.
    Rapoport, S.I. (1991). Positron emission tomography in Alzheimer’s disease in relation to disease pathogenesis: A critical review. Cerebrovasc. Brain Metab. Rev, 3, 297–335.Google Scholar
  66. 67.
    Rapoport, S.1., and Grady, C.L. (1993). Parametric in vivo brain imaging during activation to examine pathological mechanisms of functional failure in Alzheimer’s disease. Int. J. Neurosci., 70, 39–56.PubMedCrossRefGoogle Scholar
  67. 68.
    Rapoport, S.I., Horwitz, B., Grady, C.L., Haxby, J.V., and Schapiro, M.B. Alzheimer’s disease, a disease of the association neocortices and connected regions: Metabolic, cognitive and pathologic correlations.ln H.J. Altman, and B. Altman (Eds), Alzheimer’s and Parkinson’s diseases. Recent Aduances in Research and Clinical Management. Plenum Press, New York. 1989, pp 115–136.Google Scholar
  68. 69.
    Rapoport, S.I., Hatanpää, K., Brady, D.R. and Chandrasekaran, K. (1997) Brain energy metabolism, cognitive function, and down-regulated oxidative phosphorylation in Alzheimer’s disease, J. Neurodegene ration, 5, 473–476.CrossRefGoogle Scholar
  69. 70.
    Scarpulla, R. (1996). Nuclear respiratory factors and the pathways of nuclear-mitochondrial interaction. Trends Cardiovasc. Med., 6, 39–45.PubMedCrossRefGoogle Scholar
  70. 71.
    Schagger, H., and Ohm, T.G. (1995). Human diseases with defects in oxidative phosphorylation. 2. FIFO ATP-synthase defects in Alzheimer’s disease revealed by blue native polyacrylamide gel electrophoresis. Eur J. Biochem., 227, 916–921.PubMedCrossRefGoogle Scholar
  71. 72.
    Scheff, S.W., DeKosky, S.T., and Price, D.A. (1990). Quantitative assessment of cortical synaptic density in Alzheimer’s disease. Neurohiol. Aging., II, 29–37.Google Scholar
  72. 73.
    Shadel, G.S., and Clayton, D.A. (1993). Mitochondrial transcription initiation. Variation and conservation. J. Biol. Chem., 268, 16083–16086.PubMedGoogle Scholar
  73. 74.
    Shoffner, J.B., Brown, M.D., Torroni, A., Lott, M.T., abell, M.F., Mirra, S.S., Beal, M.F., Yang,C.C., Gearing, M., Salvo, R., Watts, R.L., Juncos, J.L., Hansen, L.A., Crain, B.J., Fayad, M., Reckord,.L., and Wallace, D.C. (1993). Mitochondrial DNA variants observed in Alzheimer’s disease and Parkinson disease patients. Genomics, 17, 171–184.Google Scholar
  74. 75.
    Simonian, N.A., and Hyman, B.T. (1993). Functional alterations in Alzheimer’s disease: Diminution of cytochrome oxidase in the hippocampal formation, J. Neuropathol. Exp. Neun l., 52, 580–585.CrossRefGoogle Scholar
  75. 76.
    Simonian, N.A., and Hyman, B.T. (1994). Functional alterations in Alzheimer’s disease: selective loss of mitochondrial-encoded cytochrome oxidase mRNA in the hippocampal formation, J. Neuropathol. Exp. Neurol., 53, 508–512.PubMedCrossRefGoogle Scholar
  76. 77.
    Sims, N.R., Finegan, J.M., Blass, J.P., Bown, D., and Neary, D. (1987). Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res., 436, 30–38.PubMedCrossRefGoogle Scholar
  77. 78.
    Sokoloff, L. (1991). Relationship between functional activity and energy metabolism in the nervous system: Whether, where and why. In N.A. Lassen, D.H. Ingvar, M.E. Raichle, and L. Friberg (eds). Brain Work and Mental Activity. Quantitative Studies with Radioactive Tracers. Alfred Benson Symposium VIII. Munksgaard. Copenhagen. pp. 52–67.Google Scholar
  78. 79.
    Suzuki, H., Hosokawa, Y., Nishikimi, M., and Ozawa, T. (1991). Existence of common homologous elements in the transcriptional regulatory regions of human nuclear genes and mitochondrial gene for the oxidative phosphorylation system. J. Biol. Chem., 266, 2333–2338.PubMedGoogle Scholar
  79. 80.
    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.PubMedCrossRefGoogle Scholar
  80. 81.
    Virbasius, C.A., Virbasius, J.V., and Scarpulla, R.C. (1993). NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev., 7, 2431–2445.PubMedCrossRefGoogle Scholar
  81. 82.
    Virbasius, J.V., and Scarpulla, R.C. (1994). Activation of the human mitochondrial 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.PubMedCrossRefGoogle Scholar
  82. 83.
    Virbasius, J.V., Virbasius, C.A., and Scarpulla, R.C. (1993). Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promotors. Genes Dev., 4, 380–392.CrossRefGoogle Scholar
  83. 84.
    Wallace, D.C. (1992). Mitochondrial genetics: A paradigm for aging and degenerative diseases. Science, 256, 628–632.PubMedCrossRefGoogle Scholar
  84. 85.
    Wolitzky, B.A., and Fambrough, D.M. (1986). Regulation of the (Na- + K-)-ATPase in cultured chick skeletal muscle. Modulation of expression by the demand for ion transport. J. Biol. Chem., 261, 9990–9999.PubMedGoogle Scholar
  85. 86.
    Wong-Riley, M.T.T. (1989). Cytochrome oxidase: An endogenous metabolic marker for neuronal activity. Trends Neurosci., 12, 94–101.PubMedCrossRefGoogle Scholar
  86. 87.
    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 Res., 141, 185–192.PubMedCrossRefGoogle Scholar
  87. 88.
    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 cytochrome oxidase technique. Ann. Otol. Rhinol. Latyngol., 90 (Suppl.2): 30–32.Google Scholar
  88. 89.
    Wong-Riley, M.T.T., and Welt, C. (1980). Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice. Proc. Natl. Acad. Sci. USA.. 77, 2333–2337.PubMedCrossRefGoogle Scholar
  89. 90.
    Wragg, M.A., Talbot, C.J., Morris, J.C., Lendon, C.L., and Goate, A.M. (1995). No association found between Alzheimer’s disease and a mitochondrial tRNA glutamine gene variant. Neurosci. Lett., 201, 107–110.PubMedCrossRefGoogle Scholar
  90. 91.
    Yen, T.-C., Su, J.-H., King, K.-L., Wei, Y.-H. (1991). Ageing associated 5 kb deletion in human liver mitochondrial DNA. Biochem. Biophys. Res. Commun., 178, 124–131PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Krish Chandrasekaran
    • 1
  • Kimmo Hatanpää
    • 2
  • Li-Ing Liu
    • 2
  • Stanley I. Rapoport
    • 2
  1. 1.Department of Anatomy and Cell BiologyUniformed University of Health SciencesBethesdaUSA
  2. 2.Laboratory of NeurosciencesNational Institute on Aging National Institutes of HealthBethesdaUSA

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