Mitochondrial Dysfunction in Chronic Fatigue Syndrome

  • Brad Chazotte


Understanding of mitochondrial dysfunction in CFS will clearly benefit from more study. Our findings warrant detailed studies on larger patient and control populations. The siting of mitochondrial impairment may lead to approaches for alleviating some of the symptoms of CFS. Studies on the effects of cytokines on cellular and mitochondrial bioenergetics are important to see whether cytokines or similar molecules are involved in linking CFS immune disturbances to mitochondrial dysfunction, and to better understand the consequences of cytokine therapies for cancer and viral infection.


Mitochondrial Dysfunction Chronic Fatigue Syndrome Chronic Fatigue Syndrome Patient Mitochondrial Myopathy Mononuclear Leukocyte 
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  1. Adamson, G. M., and Billings, R. E., 1992, Tumor necrosis factor induced oxidative stress in isolated mouse hepatocytes, Arch. Biochem. Biophys. 294:223–229.CrossRefPubMedGoogle Scholar
  2. Aoki, T., Miyakoshi, H., Usuda, Y., and Hernerman, R. B., 1993, Low NK syndrome and its relationship to chronic fatigue syndrome, Clin. Immunol. Immunopath. 69:253–265.CrossRefGoogle Scholar
  3. Barbiroli, B., Montagna, P., Martinelli, P., Lodi, R., Lotti, S., Cortelli, P., Funicello, R., and Zaniol, P., 1993, Defectivebrainenergymetabolism by in vivo3lpmr spectroscopy in 28 patients with mitochondrial cytopathies, J. Cereb. Blood Flow Metab. 13:469–474.PubMedGoogle Scholar
  4. Barke, R. A., Brady, P. S., and Brady, L. J., 1991, The Ca2+ second messenger system and interleukin-I-alpha modulation of hepatic gene transcription and mitochondrial fat oxidation, Surgery 110:285–294.PubMedGoogle Scholar
  5. Behan, W. H. M., More, A.R., and Behan, P. O., 1991, Mitochondrial abnormalities in the postviral fatigue syndrome, Acta Neuropathol. 83:61–65.CrossRefPubMedGoogle Scholar
  6. Bengtsson, A, and Henriksson, K. G., 1989, The muscle in fibromyalgia: A review of Swedish studies, J. Rheumatol. 16:144–149.Google Scholar
  7. Bock, G. R., and Whelan, J. (Eds.), 1993, Chronic Fatigue Syndrome, Ciba Foundation Symposium 173, Wiley, Chichester, England.Google Scholar
  8. Buchwald, D., 1991, Laboratory abnormalities in chronic fatigue syndrome, in PostViral Fatigue Syndrome (R. Jenkins and J. Mobray, Eds.), Wiley, Sussex, England, pp. 117–136.Google Scholar
  9. Buchwald, D., and Komaroff, A.L., 1991, Review of laboratory findings for patients withchronic fatigue syndrome, Rev. Infect. Dis. 13:S12–18.PubMedGoogle Scholar
  10. Buchwald, D., Umali, P., Kith, P., Perlman, B. A., and Komaroff, A. L., 1995, Chronic fatigue and chronic fatigue syndrome: Prevalence in a Pacific Northwest health care system, Ann. Int. Med. 123:81–88.PubMedGoogle Scholar
  11. Caligiuri, M., Murray, C., Buchwald, D., Levine, H., Cheney, P., Peterson D., Komaroff, A. L., and Ritz, J., 1987, Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome, J. Immunol. 139:3306–3313.PubMedGoogle Scholar
  12. Cannon, J. G., Angel, J. B., Abad, L. W., Vannier, E., Mileno, M. D., Fagioli, L., Wolff, S. M., and Komaroff, A. L., 1997, Interleukin-1β interleukin-1 receptor antagonist, and soluble interleukin-lreceptor type II secretion in chronic fatigue syndrome, J. Clin. Immunol. 17:253–261.CrossRefPubMedGoogle Scholar
  13. Carofoli, E., and Roman, I., (1980), Mitochondria and disease, Mol Aspects Med. 3:297–400.Google Scholar
  14. Chacon, E., Reece, J. M., Nieminen, A.-L., Zahrebelski, G., Herman, B., and Lemasters, J. J., 1994, Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit myocytes during chemical hypoxia: A multiparameter digitized confocal microscopic study, Biophys. J. 66:942–952.PubMedGoogle Scholar
  15. Chazotte, B., and Pettengill, M., 1998, Cytokine effects on mitochondrial membrane potential and possible mitochondrial dysfunction in chronicfatigue and immune dysfunction syndrome, ASBMB J. May 1998.Google Scholar
  16. Chazotte, B., and Pettengill, M., 1999, Using membrane potential to follow cytokinc effects on mitochondria and possible dysfunction in chronic fatigue syndrome, Biophys. J. 76:A363.Google Scholar
  17. Chazotte, B., Loehr, J.P., and Hackenbrock, C.R., 1996, Quantitative analyses of membrane potential of mitochondria in individual living human cells related to chronic illness, FASEB J. 10:A1377.Google Scholar
  18. Cheney, P., and Lapp, C. W., 1992, The diagnosis of chronic fatigue syndrome: An assertive approach, CFIDS Chronicle Physician’s Forum, Sept. 13–19.Google Scholar
  19. Cho, W. K., and Stollerman, G. H., 1992, Chronic fatigue syndrome, Hospital Practice Sept 15 27:221–245.PubMedGoogle Scholar
  20. Coates, P. M., Hale, D. E., Stanley, C. A., Corkey, B. E. and Cortner, J. A., 1985, Genetic deficiency of medium-chain Acyl-Co A dehyrogenase: Studies in cultured skin fibroblasts and peripheral mononuclear leukocytes, Pediat. Res. 19:671–676.PubMedGoogle Scholar
  21. Dawson, D. M., and Sabin, T. D. (Eds.), Chronic Fatigue Syndrome, Little, Brown, Boston, 1993.Google Scholar
  22. Demitrack, M. A., 1994, Neuroendocrine aspects of chronic fatigue syndrome: Implications for diagnosis and research, in Chronic Fatigue Syndrome (S. E. Straus, Ed.), Marcel Dekker, New York.Google Scholar
  23. Demitrack, M. A., and Crofford, L. J., 1998, Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation infibromyalgia and chronic fatigue syndrome, Ann. NY Acad. Sci. 840:684–697.PubMedGoogle Scholar
  24. DiMauro, S., Bonillia, E., Zeviani, M., Nakagawa, M., and DeVivo, D. C., 1985, Mitochondrial myopathies, Annu. Neurol. 17:521–538.Google Scholar
  25. Frackowiak, R. S. J., Herold, S., Petty, R. K. H., and Morgan-Hughes, J. A., 1988, The cerebral metabolism of glucose and oxygenmeasured withpositron tomography in patients withmitochondrialdiseases, Brain 111:1009–1024.PubMedGoogle Scholar
  26. Fukuda, K., and Gantz, N. M., 1995, Management strategies for chronic fatigue syndrome, Fed. Pract. July.Google Scholar
  27. Fukuda, K., Straus, S. E., Hickie, I., Sharpe, M. C., Dobbins, J. G., and Komaroff, A., 1994, The chronic fatigue syndrome: A comprehensive approach to its definition and study, Ann. Intern. Med. 121:953–959.PubMedGoogle Scholar
  28. Geng, Y.-j., Hansson, G. K., and Holme, E., 1992, Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells, Circ. Rex. 71:1268–1276.Google Scholar
  29. Grafman, J., Johnson, R., and Scheffers, M., 1991, Cognitive and mood-state changes in patients with chronic fatigue syndrome, Rev. Infect. Dis. 13:S45–S52.PubMedGoogle Scholar
  30. Gunn, W. J., Connell, O. B., and Randell, B., 1993, Epidemiology of chronic fatigue syndrome: The Centers for Disease Control Study, in Chronic Fatigue Syndrome, (G. R. Bock and J. Whelan, Eds.), CIBA Foundation Symposium 173, Wiley, Chichester, England, pp. 83–108.Google Scholar
  31. Ho-Yen, D. O., Carrington, D., and Armstrong, A. A., 1988, Myalgic encephalomyelitis and alpha-interferon, Lancet i:125–127.Google Scholar
  32. Holms, G. P., Kaplan, J. E., Gantz, N. M., Komaroff, A. L., Schonberger, L. B., Straus, S. E., Jomes, J. F., Dubois, R. E., Cunningham-Rundles, C., Pahwa, S., Tosato, G., Zegans, L. S., Purtilo, D. T., Brown, N., Schooley, R. T., and Brus, 1., 1998, Chronic fatigue syndrome: A working case definition, Ann. Intern. Med. 108: 387–389.Google Scholar
  33. Hyde, B. M., and Jain, A., 1992, Clinical observations of CNS dysfunction in post-infectious, acute onset M.E./C.F.S., in The Clinical and Scientific Basis of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (B. M. Hyde, J. A. Goldstein, P. H. Levine, Eds.), the Nightingale Foundation, Ottawa, Canada, pp. 38–57.Google Scholar
  34. Hyde, B. M., Goldstein, J. A., and Levine, P. H. (Eds.), The Clinical and Scientific Bash of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, The Nightingale Foundation, Ottawa, Canada.Google Scholar
  35. Gunn, W. J., Connell, D. B., and Randell, B., 1993, Epidemiology Chronic Fatigue Syndrome: The Centers for Disease Control Study In Chronic Fatigue Syndrome, (G. R. Bock and J. Whelan, eds.), Ciba Foundation Symposium’ 93. Wiley, Chichester, England.Google Scholar
  36. Jamal, G. A., and Hansen, S., 1985, Electrophysiological studies in the post-viral fatigue syndrome, J. Neurol, Neuorsurg. Psychiat. 48:691–694.Google Scholar
  37. Jenkins, R., and Mowbray, J. (Eds), 1991, Post-Viral Fatigue Syndrome, Wiley, Chichester, England.Google Scholar
  38. Jones, J. F., 1991, Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus, Rev. Inject. Dis. 13:S26–S31.Google Scholar
  39. Kartounis, L. D., Troung, D. D., Morgan-Hughes, J. A., and Harding, A. E., 1992, The neuropsychological features of mitochondrial myopathies and encephalopathies, Arch. Neurol. 49:158–160.Google Scholar
  40. Klimas, N. G., Salvato, F. R., Morgan, R., and Fletcher, M. A., 1990, Immunologic abnormalities in chronic fatigue syndrome, J. Clin. Microbiol. 28:1403–1410.PubMedGoogle Scholar
  41. Komaroff, A. L., 1997, A 56-year-old woman with chronic fatigue syndrome, JAMA 278:1179–1185.CrossRefPubMedGoogle Scholar
  42. Komaroff, A. L., and Buchwald, D. S., 1998, Chronic fatigue syndrome: An update, Annu. Rev. Med. 49: 1–13.PubMedGoogle Scholar
  43. Kruit, W. H., Punt, K. J., Goey, S. H., de Mulder, p. H., van Hoogenhuyze, D. C., Henzen-Logmans, W, and Stoter, G., 1994, Cardiotoxicity as a dose-limiting factor in a schedule of high dose bolus therapy with interleukin-2 and alpha-interferon, Cancer 74:2850–2856.PubMedGoogle Scholar
  44. Kuratsume, H., Yamaguti, K., Takahashi, M., Misaki, H., Tagawa, S., and Kitani, T., 1994, Acylcarnitine deficiency in chronic fatigue syndrome, Clin. Infect. Dis. 18:S62–S67.Google Scholar
  45. Lane, R. J. M., Burgess, A. P., Flint, J., Riccio, M., and Archard, L. C., 1995, Exercise responses and psychiatric disorder chronic fatigue syndrome, Brit. Med. J. 311:544–545.PubMedGoogle Scholar
  46. Lane, R. J. M., Barrett, M. C., Taylor, D. J., Kemp, G. J., and Lodi, R., 1998a, Heterogeneity in chronic fatigue syndrome: Evidence from magnetic resonance spectroscopy of muscle, Neuromus. Disord. 8:204–209.Google Scholar
  47. Lane, R. J. M., Barrett, M. C., Woodrow, D., Moss, J., Fletcher, R., and Archard, L. C., 1998b, Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome, J. Neurol. Neurosurg. Psychiat. 64:362–367.PubMedGoogle Scholar
  48. Lemasters, J. J., Chacon, E., Zahrebelski, G., Reece, J. M., and Nieminen, A.-L., 1993a, Laser scanning confocal microscopy of living cells, in Optical Microscopy: Emerging Methods and Applications (B. Herman and J. J. Lemasters, Eds), Plenum, New York, pp 339–354.Google Scholar
  49. Lemasters, J. J., Nieminen, A.-L., Chacon, E., Imberti, R., Gores, G. J., Reece, J. M., and Herman, B., 1993b, Use of fluorescent probes to monitor mitochondrial membrane potential in isolated mitochondria, cell suspensions, and cultured cells, in Mitochondrial Dysfunction Methods in Toxicology, Vol. 2 (L. H. Lash, and D. P. Jones, Eds.), Academic, New York, pp. 404–415.Google Scholar
  50. Lever, A. M. L., Lewis, D. M., Bannister, B. A., Fry, M., and Berry, N., 1988, Interferon production in postviral fatigue syndrome, Lancet ii:l01.Google Scholar
  51. Levy, J. A., 1994, Viral studies of chronic fatigue syndrome, Clin. Infect. Dis. 18:S117–S120.PubMedGoogle Scholar
  52. Lloyd, A., Hickie, I., Brockman, A., Dwyer, J., and Wakefield, D., 1991, Cytokine levels in serum and cerebrospinal fluid in patients with chronic fatigue syndrome, J. Infect. Dis. 164:1023–1024.PubMedGoogle Scholar
  53. MacDonald, E., 1987, Interferons as mediators of psychiatric morbidity; An investigation in a trial of recombinant alpha-interferon in hepatitis-B carriers, Lancer ii: 1175–1178.Google Scholar
  54. McCully, K. K.., Natelson, B. H., Lotti, S., Sisto, S., Leigh, J. S., 1996, Reduced oxidative metabolism in chronic fatigue syndrome, Muscle and Nerve 19:621–625.CrossRefPubMedGoogle Scholar
  55. McGregor, N. R., Dunstan, R. H., Zerbes, M, Butt, H. L., Roberts, T. K., and Klineberg, I. J., 1996, Preliminary determination of a molecular basis to chronic fatigue syndrome, Biochem. Mol. Med. 57:73–80.CrossRefPubMedGoogle Scholar
  56. Montague, T. J., Marrie, T. J., Klassen, G. A., Bewick, D. J., and Horacek, B. M,, 1989, Cardiac function at rest and with exercise in the chronic fatigue syndrome, Chest 95:779–784.PubMedGoogle Scholar
  57. Nakagawa, K., Miller, F. N., Sims, D. E., Lentsch, A. B., Miyazaki, M., and Edwards, M. J., 1996, Mechanisms of interleukin-2 hepatic toxicity, Cancer Rex. 56:507–510.Google Scholar
  58. Natelson, B. H., Cohen, J. M., Brassloff, I., and Lee, H. J., 1993, A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J. Neural. Sci. 120:203–207.Google Scholar
  59. Ojo-Amaze, H. A., Conley, E. J., and Peter, J. B., 1994, Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome, Clin. Infect. Dis. 18:S157–S159.Google Scholar
  60. Pawley J. B., Handbook of Biological Confocal Microscopy, 2nd ed., Plenum, New York, 1995.Google Scholar
  61. Peterson, P. L., 1995, The treatment of mitochondrial myopathies and encephalomyopathies, Biochim. Biophys. Acta 1271:275–280.PubMedGoogle Scholar
  62. Petit, P. X., O’Conner, J. E., Grunwald, D., and Brown, S. C., 1990, Analysis of the membrane potential of rat-and mouse-liver mitochondria by flow cytometry and possible applications, Eur. J Biochem. 193:389–397.Google Scholar
  63. Plioplys, A. V, and Plioplys, S., 1997, Amantadine and L-carnitine treatment of chronic fatigue syndrome, Neuropsychobio. 35:16–23.Google Scholar
  64. Rasmussen, H., Nielsen, H., Andersen, V, Barington, T., Bendtzen, K.., Hansen, S., Nielsen, L., Pedersen, B. K.., and Wiik, A., 1994, Chronic fatigue syndrome: A controlled cross-sectional study, J. Rheumatol. 21:1527–1531.PubMedGoogle Scholar
  65. Reyes, M., Gary, H. E., Jr., Dobbins, J. G., Randall, B., Steele, L., Fukuda, K.., Holms, G. P., Connell, D. G., Mawle, A. C., Schmid, D. S., Stewart, J. A., Schonberger, L. B., Gunn, W. J., and Reeves, W. C., 1997, Surveillance for chronic fatigue syndrome: Four U. S. cities, September 1989 through August 1993, MMWR 46:1–13.PubMedGoogle Scholar
  66. Roe, C.R., and Coates, P. M., 1989, Acyl-CoA dehydrogenase deficiencies, in Metabolic Bases of Inherited Disease, 6th ed. (C. R., Scribner, A. L. Beaudet, W. A. Sly, and D. Valle Eds.), McGraw-Hill, NY, pp. 889–914.Google Scholar
  67. Rowe, P. C., Bou-Holaigah, I., Kan, J. S., and Calkins, H., 1995, Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet 345:623–624.PubMedGoogle Scholar
  68. Sandman, C. A., Barron, J. L., Nackoul, K.., Goldstein, J., and Fidler, F., 1993, Memory deficits associated with chronic fatigue immune dysfunction syndrome, Biol. Psychiat, 33:618–623.PubMedGoogle Scholar
  69. Schwartz, R. B., Garada, B. M., Komaroff, A. L., Tice, H. M., Gleit, M., Jolez, F. A., and Holman, B. L., 1993a, Detection of intracranial abnormalities in patients with chronic fatigue syndrome: Comparison of MR imaging and SPECT, Am. J. Rad. 162:935–941.Google Scholar
  70. Schwartz, R. B., Komaroff, A. L., Garada, B. M., Gleit, M., Doolittle, T. H., Bates, D. W., Vasile, R. G., and Holman, B. L., 1993b, SPECT imaging of the brain: Comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression, Am. J. Rad. 162:943–951.Google Scholar
  71. Straus, S. E., 1988, The chronic mononucleosis syndrome, J. Infect. Dis. 157:405–412.PubMedGoogle Scholar
  72. Straus, S. E. (Ed.), 1994, Chronic Fatigue Syndrome, Marcel Dekker, New York.Google Scholar
  73. Vojdani, A., Ghoneum, M., Choppa, P. C., Magatoto, L., and Lapp, C. W., 1997, Elevatedapoptotic cell population in patients with chronic fatigue syndrome: The pivotal role of protein kinase RNA, J. Int. Med. 242:465–478.Google Scholar
  74. Wallace, D. A., 1992, Mitochondrial DNA diseases, Ann. Rev. Biochem. 61:1175–1212.PubMedGoogle Scholar
  75. Wong, R., Lopaschuk, G., Zhu, G., Walker, D., Catellier, D., Burton D., Teo, K. Collins-Nakai, R., and Montague, T, 1992. Skeletal muscle metabolism in the chronic fatigue syndrome. Chest 102:1716–1722.PubMedGoogle Scholar
  76. Zar, J. H., 1985, Biostatistical Analysis, 2nd ed., Prentice-Hall, Englewood Cliffs, New JerseyGoogle Scholar
  77. Zhang, C., Baumer, A., Mackay, I. R., Linnane, A. W., and Nagley, P., 1995, Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome, Hum. Mol. Genet. 4:751–754.PubMedGoogle Scholar

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© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Brad Chazotte
    • 1
  1. 1.Department of Pharmaceutical SciencesCampbell UniversityBuies Creek

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