Molecular Neurobiology

, Volume 48, Issue 3, pp 883–903 | Cite as

Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications

  • Gerwyn Morris
  • George Anderson
  • Michael Berk
  • Michael Maes


Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital cofactor in the mitochondrial electron transport chain, enabling the generation of adenosine triphosphate. It additionally regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins; and has anti-inflammatory, redox modulatory, and neuroprotective effects. This paper reviews the known physiological role of CoQ10 in cellular metabolism, cell death, differentiation and gene regulation, and examines the potential repercussions of CoQ10 depletion including its role in illnesses such as Parkinson’s disease, depression, myalgic encephalomyelitis/chronic fatigue syndrome, and fibromyalgia. CoQ10 depletion may play a role in the pathophysiology of these disorders by modulating cellular processes including hydrogen peroxide formation, gene regulation, cytoprotection, bioenegetic performance, and regulation of cellular metabolism. CoQ10 treatment improves quality of life in patients with Parkinson’s disease and may play a role in delaying the progression of that disorder. Administration of CoQ10 has antidepressive effects. CoQ10 treatment significantly reduces fatigue and improves ergonomic performance during exercise and thus may have potential in alleviating the exercise intolerance and exhaustion displayed by people with myalgic encepholamyletis/chronic fatigue syndrome. Administration of CoQ10 improves hyperalgesia and quality of life in patients with fibromyalgia. The evidence base for the effectiveness of treatment with CoQ10 may be explained via its ability to ameliorate oxidative stress and protect mitochondria.


Coenzyme Q10 Oxidative and nitrosative stress Inflammation Cytokines Mitochondria 



Coenzyme Q10


Adenosine triphosphate


Reactive oxygen species


Reactive nitrogen species


Oxidative and nitrosative stress


Nuclear factor-κB




Superoxide dismutase


Myalgic encepholamyletis/chronic fatigue syndrome


Parkinson’s disease


Nitric oxide




Poly-unsaturated fatty acids


Ubiquitin–proteasome system




Peroxisome proliferator-activated receptor (PPAR) gamma co-activator-1 alpha


Uncoupler protein


Nuclear factor (erythroid-derived 2)-like 2


Antioxidant response element


Mitochondrial DNA


Nuclear respiratory factor 1/2


Tumor necrosis factor








Cardiovascular disorder


Forward rate constant


Unified Parkinson Disease Rating Scale


Competing interests

No specific funding was obtained for this specific review. MBk has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma and Servier; has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth; and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck; and Servier. GM, AG, and MM declare that they have no competing interests.


  1. 1.
    Jelin JM, Gregory PJ et al (2009) Natural medicines comprehensive database/compiled by the editors of Pharmacist’s Letter, Prescriber’s Letter, 11th edn. Therapeutic Research Faculty, Stockton, CA, pp 452–457Google Scholar
  2. 2.
    Fetrow CW, Avila JR (2001) Professional’s handbook of complementary & alternative medicines, 2nd edn. Springhouse, Springhouse, PA, pp 211–215Google Scholar
  3. 3.
    Berthold HK, Naini A, Di Mauro S, Hallikainen M, Gylling H, Krone W, Gouni-Berthold I (2006) Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial. Drug Saf 29(8):703–712PubMedGoogle Scholar
  4. 4.
    Littarru GP, Tiano L (2007) Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol 37(1):31–37PubMedGoogle Scholar
  5. 5.
    Ikematsu H, Nakamura K, Harashima S, Fujii K, Fukutomi N (2006) Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trial. Regul Toxicol Pharmacol 44(3):212–218PubMedGoogle Scholar
  6. 6.
    Crane FL (2008) The evolution of coenzyme Q. Biofactors 32(1–4):5–11PubMedGoogle Scholar
  7. 7.
    De Cabo R, Cabello R, Rios M, López-Lluch G, Ingram DK, Lane MA, Navas P (2004) Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver. Exp Gerontol 39(3):297–304PubMedGoogle Scholar
  8. 8.
    Navarro F, Villalba JM, Crane FL, Mackellar WC, Navas P (1995) A phospholipid-dependent NADH-coenzyme Q reductase from liver plasma membrane. Biochem Biophys Res Commun 212(1):138–143PubMedGoogle Scholar
  9. 9.
    Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A 95(15):8892–8897PubMedCentralPubMedGoogle Scholar
  10. 10.
    Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20(6):591–598PubMedGoogle Scholar
  11. 11.
    Potgieter M, Pretorius E, Oberholzer HM (2009) Qualitative electron microscopic analysis of cultured chick embryonic cardiac and skeletal muscle cells: the cellular effect of coenzyme q10 after exposure to triton x-100. Ultrastruct Pathol 33(3):93–101PubMedGoogle Scholar
  12. 12.
    Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Doring F (2008) Functions of coenzyme Q10 in inflammation and gene expression. Biofactors 32(1–4):179–183PubMedGoogle Scholar
  13. 13.
    Bentinger M, Tekle M, Dallner G (2010) Coenzyme Q—biosynthesis and functions. Biochem Biophys Res Commun 396(1):74–79PubMedGoogle Scholar
  14. 14.
    Groneberg DA, Kindermann B, Althammer M, Klapper M, Vormann J, Littarru GP, Döring F (2005) Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int J Biochem Cell Biol 37(6):1208–1218PubMedGoogle Scholar
  15. 15.
    Schmelzer C, Döring F (2010) Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes. Biofactors 36(3):222–228PubMedGoogle Scholar
  16. 16.
    Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA (2004) The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. Free Radic Biol Med 36(8):1043–1057PubMedGoogle Scholar
  17. 17.
    Wyman M, Leonard M, Morledge T (2010) Coenzyme Q10: a therapy for hypertension and statin-induced myalgia? Cleve Clin J Med 77(7):435–442PubMedGoogle Scholar
  18. 18.
    Schmelzer C, Lindner I, Vock C, Fujii K, Döring F (2007) Functional connections and pathways of coenzyme Q10-inducible genes: an in-silico study. IUBMB Life 59(10):628–633PubMedGoogle Scholar
  19. 19.
    Schmelzer C, Lorenz G, Rimbach G, Döring F (2007) Influence of coenzyme Q{10} on release of pro-inflammatory chemokines in the human monocytic cell line THP-1. Biofactors 31(3–4):211–217PubMedGoogle Scholar
  20. 20.
    Schmelzer C, Lorenz G, Rimbach G, Döring F (2009) In vitro effects of the reduced form of coenzyme Q(10) on secretion levels of TNF-alpha and chemokines in response to LPS in the human monocytic cell line THP-1. J Clin Biochem Nutr 44(1):62–66PubMedCentralPubMedGoogle Scholar
  21. 21.
    Barroso MP, Gómez-Díaz C, Villalba JM, Burón MI, López-Lluch G, Navas P (1997) Plasma membrane ubiquinone controls ceramide production and prevents cell death induced by serum withdrawal. J Bioenerg Biomembr 29(3):259–267PubMedGoogle Scholar
  22. 22.
    González R, Ferrín G, Hidalgo AB, Ranchal I, López-Cillero P, Santos-Gónzalez M, López-Lluch G, Briceño J, Gómez MA, Poyato A, Villalba JM, Navas P, de la Mata M, Muntané J (2009) N-acetylcysteine, coenzyme Q10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes. Chem Biol Interact 181(1):95–106PubMedGoogle Scholar
  23. 23.
    Kon M, Kimura F, Akimoto T, Tanabe K, Murase Y, Ikemune S, Kono I (2007) Effect of coenzyme Q10 supplementation on exercise-induced muscular injury of rats. Exerc Immunol Rev 13:76–88PubMedGoogle Scholar
  24. 24.
    Wang H, Zhao X, Yin S (2008) Effects of coenzyme Q10 or combined with micronutrients on antioxidant defense system in rats. Wei Sheng Yan Jiu 37(3):311–313PubMedGoogle Scholar
  25. 25.
    González-Aragón D, Burón MI, López-Lluch G, Hermán MD, Gómez-Díaz C, Navas P, Villalba JM (2005) Coenzyme Q and the regulation of intracellular steady-state levels of superoxide in HL-60 cells. Biofactors 25(1–4):31–41PubMedGoogle Scholar
  26. 26.
    Hiebert JB, Shen Q, Pierce JD (2012) Application of coenzyme Q10 in clinical practice. Int J Intern Med. doi: 10.5580/2b24 Google Scholar
  27. 27.
    Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, Dimauro S, Hirano M (2006) A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet 78(2):345–349PubMedCentralPubMedGoogle Scholar
  28. 28.
    López LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJ, Naini A, Dimauro S, Hirano M (2006) Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 79(6):1125–1129PubMedCentralPubMedGoogle Scholar
  29. 29.
    DiMauro S, Quinzii CM, Hirano M (2007) Mutations in coenzyme Q10 biosynthetic genes. J Clin Invest 117(3):587–589PubMedCentralPubMedGoogle Scholar
  30. 30.
    Fischer A, Schmelzer C, Rimbach G, Niklowitz P, Menke T, Döring F (2011) Association between genetic variants in the coenzyme Q10 metabolism and coenzyme Q10 status in humans. BMC Res Notes 4:245PubMedCentralPubMedGoogle Scholar
  31. 31.
    Abe K, Fujimura H, Nishikawa Y, Yorifuji S, Mezaki T, Hirono N, Nishitani N, Kameyama M (1991) Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Acta Neurol Scand 83(6):356–359PubMedGoogle Scholar
  32. 32.
    Bresolin N, Bet L, Binda A, Moggio M, Comi G, Nador F, Ferrante C, Carenzi A, Scarlato G (1988) Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q10. Neurology 38(6):892–899PubMedGoogle Scholar
  33. 33.
    Shoffner JM, Lott MT, Voljavec AS, Soueidan SA, Costigan DA, Wallace DC (1989) Spontaneous Kearns–Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci U S A 86(20):7952–7956PubMedCentralPubMedGoogle Scholar
  34. 34.
    Kurup RK, Kurup PA (2003) Isoprenoid pathway dysfunction in chronic fatigue syndrome. Acta Neuropsychiatr 15(5):266–273Google Scholar
  35. 35.
    Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009) Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett 30(6):715–722PubMedGoogle Scholar
  36. 36.
    Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009) Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 30(4):470–476PubMedGoogle Scholar
  37. 37.
    Cordero MD, Cano-García FJ, Alcocer-Gómez E, De Miguel M, Sánchez-Alcázar JA (2012) Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q10 effect on clinical improvement. PLoS One 7(4):e35677PubMedCentralPubMedGoogle Scholar
  38. 38.
    Cordero MD, Cotán D, del-Pozo-Martín Y, Carrión AM, de Miguel M, Bullón P, Sánchez-Alcazar JA (2012) Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient. Nutrition 28(11–12):1200–1203PubMedGoogle Scholar
  39. 39.
    Forester BP, Zuo CS, Ravichandran C, Harper DG, Du F, Kim S, Cohen BM, Renshaw PF (2012) Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression. J Geriatr Psychiatry Neurol 25(1):43–50PubMedGoogle Scholar
  40. 40.
    Shults CW, Haas RH, Passov D, Beal MF (1997) Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 42(2):261–264PubMedGoogle Scholar
  41. 41.
    Beal MF (2002) Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic Res 36(4):455–460PubMedGoogle Scholar
  42. 42.
    Beal MF (2004) Therapeutic effects of coenzyme Q10 in neurodegenerative diseases. Methods Enzymol 382:473–487PubMedGoogle Scholar
  43. 43.
    Dhanasekaran M, Ren J (2005) The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus. Curr Neurovasc Res 2(5):447–459PubMedGoogle Scholar
  44. 44.
    Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2011) Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit 17(4):SC11–SC15PubMedGoogle Scholar
  45. 45.
    Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35(3):804–817PubMedGoogle Scholar
  46. 46.
    Anderson G, Maes M (2013) TRYCAT pathways link peripheral inflammation, nicotine, somatization and depression in the etiology and course of Parkinson’s disease. CNS Neurolog Dis (in press).Google Scholar
  47. 47.
    Rollins B, Martin MV, Sequeira PA, Moon EA, Morgan LZ, Watson SJ, Schatzberg A, Akil H, Myers RM, Jones EG, Wallace DC, Bunney WE, Vawter MP (2009) Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. PLoS One 4(3):e4913. doi: 10.1371/journal.pone.0004913, Epub 2009 Mar 17. PubMed PMID: 19290059; PubMed Central PMCID: PMC2654519PubMedCentralPubMedGoogle Scholar
  48. 48.
    Nierenberg AA, Kansky C, Brennan BP, Shelton RC, Perlis R, Iosifescu DV (2013) Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development. Aust N Z J Psychiatry 47(1):26–42PubMedGoogle Scholar
  49. 49.
    Shults CW (2003) Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem 10(19):1917–1921PubMedGoogle Scholar
  50. 50.
    Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G (2010) Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets 11(1):111–121PubMedGoogle Scholar
  51. 51.
    Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M, Parkinson Study Group (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59(10):1541–1550PubMedGoogle Scholar
  52. 52.
    Liu J, Wang L, Zhan SY, Xia Y (2011) Coenzyme Q10 for Parkinson’s disease. Cochrane Database Syst Rev 2011(12), CD008150Google Scholar
  53. 53.
    Turko IV, Marcondes S, Murad F (2001) Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase. Am J Physiol Heart Circ Physiol 281(6):H2289–H2294PubMedGoogle Scholar
  54. 54.
    Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23(5):599–622PubMedGoogle Scholar
  55. 55.
    Vega-López S, Devaraj S, Jialal I (2004) Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease. J Investig Med 52(1):24–32PubMedGoogle Scholar
  56. 56.
    Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208PubMedGoogle Scholar
  57. 57.
    Fernstrom JD (1999) Effects of dietary polyunsaturated fatty acids on neuronal function. Lipids 34(2):161–169PubMedGoogle Scholar
  58. 58.
    Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu RG (1993) Nitric oxide: an endogenous anticonvulsant substance. Neuroreport 4(4):444–446PubMedGoogle Scholar
  59. 59.
    Jenkinson AM, Collins AR, Duthie SJ, Wahle KW, Duthie GG (1999) The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes. FASEB J 13(15):2138–2142PubMedGoogle Scholar
  60. 60.
    Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochemistry 97(6):1634–1658Google Scholar
  61. 61.
    Smith JA, Park S, Krause JS, Banik NL (2013) Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration. Neurochem Int. doi: 10.1016/j.neuint.2013.02.013, Epub ahead of printPubMedGoogle Scholar
  62. 62.
    Shibata N, Kobayashi M (2008) The role for oxidative stress in neurodegenerative diseases. Brain Nerve 60(2):157–170PubMedGoogle Scholar
  63. 63.
    Farooqui T, Farooqui AA (2011) Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson’s disease. Park Dis 2011:247467Google Scholar
  64. 64.
    Nakamura T, Lipton SA (2010) Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases. Apoptosis 15(11):1354–1363PubMedCentralPubMedGoogle Scholar
  65. 65.
    Storch A, Jost WH, Vieregge P, Spiegel J, Greulich W, Durner J, Müller T, Kupsch A, Henningsen H, Oertel WH, Fuchs G, Kuhn W, Niklowitz P, Koch R, Herting B, Reichmann H, German Coenzyme Q(10) Study Group (2007) Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease. Arch Neurol 64(7):938–944PubMedGoogle Scholar
  66. 66.
    Bandyopadhyay U, Cuervo AM (2007) Chaperone-mediated autophagy in aging and neurodegeneration: lessons from alpha-synuclein. Exp Gerontol 42(1–2):120–128PubMedGoogle Scholar
  67. 67.
    Rubinsztein DC (2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443(7113):780–786PubMedGoogle Scholar
  68. 68.
    Keller JN, Dimayuga E, Chen Q, Thorpe J, Gee J, Ding Q (2004) Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int J Biochem Cell Biol 36(12):2376–2391PubMedGoogle Scholar
  69. 69.
    Grune T, Reinheckel T, Joshi M, Davies KJ (1995) Proteolysis in cultured liver epithelial cells during oxidative stress. Role of the multicatalytic proteinase complex, proteasome. J Biol Chem 270(5):2344–2351PubMedGoogle Scholar
  70. 70.
    Grune T, Blasig IE, Sitte N, Roloff B, Haseloff R, Davies KJ (1998) Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasome. J Biol Chem 273(18):10857–10862PubMedGoogle Scholar
  71. 71.
    Ullrich O, Reinheckel T, Sitte N, Grune T (1999) Degradation of hypochlorite-damaged glucose-6-phosphate dehydrogenase by the 20S proteasome. Free Radic Biol Med 27(5–6):487–492PubMedGoogle Scholar
  72. 72.
    Malkus KA, Tsika E, Ischiropoulos H (2009) Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson’s disease: how neurons are lost in the Bermuda triangle. Mol Neurodegener 4:24PubMedCentralPubMedGoogle Scholar
  73. 73.
    Friguet B, Szweda LI (1997) Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein. FEBS Lett 405(1):21–25PubMedGoogle Scholar
  74. 74.
    Friguet B, Stadtman ER, Szweda LI (1994) Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Formation of cross-linked protein that inhibits the multicatalytic protease. J Biol Chem 269(34):21639–21643PubMedGoogle Scholar
  75. 75.
    Sitte N, Merker K, Von Zglinicki T, Grune T, Davies KJ (2000) Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I—effects of proliferative senescence. FASEB J 14(15):2495–2502PubMedGoogle Scholar
  76. 76.
    Sitte N, Huber M, Grune T, Ladhoff A, Doecke WD, Von Zglinicki T, Davies KJ (2000) Proteasome inhibition by lipofuscin/ceroid during postmitotic aging of fibroblasts. FASEB J 14(11):1490–1498PubMedGoogle Scholar
  77. 77.
    Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, Mosharov EV, Hodara R, Fredenburg R, Wu DC, Follenzi A, Dauer W, Przedborski S, Ischiropoulos H, Lansbury PT, Sulzer D, Cuervo AM (2008) Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 118(2):777–788PubMedCentralPubMedGoogle Scholar
  78. 78.
    Wan FY, Wang YN, Zhang GJ (2001) The influence of oxidation of membrane thiol groups on lysosomal proton permeability. Biochem J 360(Pt 2):355–362PubMedGoogle Scholar
  79. 79.
    Brunk UT, Dalen H, Roberg K, Hellquist HB (1997) Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Radic Biol Med 23(4):616–626PubMedGoogle Scholar
  80. 80.
    Brunk UT, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33(5):611–619PubMedGoogle Scholar
  81. 81.
    Ditaranto K, Tekirian TL, Yang AJ (2001) Lysosomal membrane damage in soluble Abeta-mediated cell death in Alzheimer’s disease. Neurobiol Dis 8(1):19–31PubMedGoogle Scholar
  82. 82.
    Nakamura M, Hayashi T (1994) One- and two-electron reduction of quinones by rat liver subcellular fractions. J Biochem 115(6):1141–1147PubMedGoogle Scholar
  83. 83.
    Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271(1):195–204PubMedGoogle Scholar
  84. 84.
    Bhagavan HN, Chopra RK (2006) Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 40(5):445–453PubMedGoogle Scholar
  85. 85.
    Donnino MW, Cocchi MN, Salciccioli JD, Kim D, Naini AB, Buettner C, Akuthota P (2011) Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock. Crit Care 15(4):R189PubMedGoogle Scholar
  86. 86.
    Crane FL, Navas P (1997) The diversity of coenzyme Q function. Mol Aspects Med 18(Suppl):S1–S6PubMedGoogle Scholar
  87. 87.
    Larm JA, Vaillant F, Linnane AW, Lawen A (1994) Up-regulation of the plasma membrane oxidoreductase as a prerequisite for the viability of human Namalwa rho 0 cells. J Biol Chem 269(48):30097–30100PubMedGoogle Scholar
  88. 88.
    Morré DM, Lenaz G, Morré DJ (2000) Surface oxidase and oxidative stress propagation in aging. J Exp Biol 203(Pt 10):1513–1521PubMedGoogle Scholar
  89. 89.
    Nohl H, Jordan W (1986) The mitochondrial site of superoxide formation. Biochem Biophys Res Commun 138(2):533–539PubMedGoogle Scholar
  90. 90.
    Turrens JF, Alexandre A, Lehninger AL (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237(2):408–414PubMedGoogle Scholar
  91. 91.
    DegliEsposti M, Ballester F, Timoneda J, Crimi M, Lenaz G (1990) The oxidation of ubiquinol by the isolated Rieske iron-sulfur protein in solution. Arch Biochem Biophys 28(2):258–265Google Scholar
  92. 92.
    Trumpower BL (1981) New concepts on the role of ubiquinone in the mitochondrial respiratory chain. J Bioenerg Biomembr 13(1–2):1–24PubMedGoogle Scholar
  93. 93.
    Lenaz G (1998) Role of mitochondria in oxidative stress and ageing. Biochim Biophys Acta 1366(1–2):53–67PubMedGoogle Scholar
  94. 94.
    Navas P, Villalba JM, de Cabo R (2007) The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion 7(Suppl):S34–S40PubMedGoogle Scholar
  95. 95.
    Santos-Ocaña C, Do TQ, Padilla S, Navas P, Clarke CF (2002) Uptake of exogenous coenzyme Q and transport to mitochondria is required for bc1 complex stability in yeast coq mutants. J Biol Chem 277(13):10973–10981PubMedGoogle Scholar
  96. 96.
    Rodríguez-Hernández A, Cordero MD, Salviati L, Artuch R, Pineda M, Briones P, Gómez Izquierdo L, Cotán D, Navas P, Sánchez-Alcázar JA (2009) Coenzyme Q deficiency triggers mitochondria degradation by mitophagy. Autophagy 5(1):19–32PubMedGoogle Scholar
  97. 97.
    Schulte-Mattler WJ, Müller T, Deschauer M, Gellerich FN, Iaizzo PA, Zierz S (2003) Increased metabolic muscle fatigue is caused by some but not all mitochondrial mutations. Arch Neurol 60(1):50–58PubMedGoogle Scholar
  98. 98.
    Finsterer J (2004) Mitochondriopathies. Eur J Neurol 11(3):163–186PubMedGoogle Scholar
  99. 99.
    Tsao CY, Mendell JR (2002) Combined partial deficiencies of carnitine palmitoyltransferase II and mitochondrial complex I presenting as increased serum creatine kinase level. J Child Neurol 17(4):304–306PubMedGoogle Scholar
  100. 100.
    Andrich J, Saft C, Gerlach M, Schneider B, Arz A, Kuhn W, Müller T (2004) Coenzyme Q10 serum levels in Huntington’s disease. J Neural Transm Suppl 68:111–116PubMedGoogle Scholar
  101. 101.
    Steele PE, Tang PH, DeGrauw AJ, Miles MV (2004) Clinical laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Am J Clin Pathol 121(Suppl):S113–S120PubMedGoogle Scholar
  102. 102.
    Walker FO, Raymond LA (2004) Targeting energy metabolism in Huntington’s disease. Lancet 364(9431):312–313PubMedGoogle Scholar
  103. 103.
    Werbach MR (2000) Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 5(2):93–108PubMedGoogle Scholar
  104. 104.
    Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134(3):707–716PubMedGoogle Scholar
  105. 105.
    Beyer RE, Ernster L (1990) The antioxidant role of Coenzyme Q. In: Lenaz G, Barnobei O, Robbi A, Battino M (eds) Highlights of ubiquinone research. Taylor & Francis, London, pp 191–213Google Scholar
  106. 106.
    Kettawan A, Takahashi T, Kongkachuichai R, Charoenkiatkul S, Kishi T, Okamoto T (2007) Protective effects of coenzyme q(10) on decreased oxidative stress resistance induced by simvastatin. J Clin Biochem Nutr 40(3):194–202PubMedCentralPubMedGoogle Scholar
  107. 107.
    Kagan V, Serbinova E, Packer L (1990) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 169(3):851–857PubMedGoogle Scholar
  108. 108.
    Ernster L, Forsmark P, Nordenbrand K (1992) The mode of action of lipid-soluble antioxidants in biological membranes: relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. Biofactors 3(4):241–248PubMedGoogle Scholar
  109. 109.
    Yamamoto Y, Komuro E, Niki E (1990) Antioxidant activity of ubiquinol in solution and phosphatidylcholine liposome. J Nutr Sci Vitaminol 36(5):505–511 (Tokyo)PubMedGoogle Scholar
  110. 110.
    Landi L, Cabrini L, Fiorentini D, Stefanelli C, Pedulli GF (1992) The antioxidant activity of ubiquinol-3 in homogeneous solution and in liposomes. Chem Phys Lipids 61(2):121–130PubMedGoogle Scholar
  111. 111.
    Bentinger M, Brismar K, Dallner G (2007) The antioxidant role of coenzyme Q. Mitochondrion 7(Suppl):S41–S50PubMedGoogle Scholar
  112. 112.
    James AM, Smith RA, Murphy MP (2004) Antioxidant and prooxidant properties of mitochondrial coenzyme Q. Arch Biochem Biophys 423(1):47–56PubMedGoogle Scholar
  113. 113.
    Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K (1995) The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions. Proc Natl Acad Sci U S A 92(20):9388–9391PubMedCentralPubMedGoogle Scholar
  114. 114.
    Singh U, Devaraj S, Jialal I (2007) Coenzyme Q10 supplementation and heart failure. Nutr Rev 65(6 Pt 1):286–293PubMedGoogle Scholar
  115. 115.
    Lee BJ, Lin YC, Huang YC, Ko YW, Hsia S, Lin PT (2012) The relationship between coenzyme Q10, oxidative stress, and antioxidant enzymes activities and coronary artery disease. Scientific World Journal 2012:792756PubMedGoogle Scholar
  116. 116.
    Frei B, Kim MC, Ames BN (1990) Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci U S A 87(12):4879–4883PubMedCentralPubMedGoogle Scholar
  117. 117.
    Mordente A, Martorana GE, Santini SA, Miggiano GA, Petitti T, Giardina B, Battino M, Littarru GP (1993) Antioxidant effect of coenzyme Q on hydrogen peroxide-activated myoglobin. Clin Investig 71(8 Suppl):S92–S96PubMedGoogle Scholar
  118. 118.
    Ernster L, Forsmark-Andrée P (1993) Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71(8 Suppl):S60–S65PubMedGoogle Scholar
  119. 119.
    Weber C, Jakobsen TS, Mortensen SA, Paulsen G, Hølmer G (1994) Effect of dietary coenzyme Q10 as an antioxidant in human plasma. Mol Aspects Med 15(Suppl):S97–S102PubMedGoogle Scholar
  120. 120.
    Kunitomo M, Yamaguchi Y, Kagota S, Otsubo K (2008) Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome. J Pharmacol Sci 107(2):128–137PubMedGoogle Scholar
  121. 121.
    Ahmadvand H, Tavafi M, Khosrowbeygi A (2012) Amelioration of altered antioxidant enzymes activity and glomerulosclerosis by coenzyme Q10 in alloxan-induced diabetic rats. J Diabetes Complications 26(6):476–482PubMedGoogle Scholar
  122. 122.
    Fritz KS, Galligan JJ, Smathers RL, Roede JR, Shearn CT, Reigan P, Petersen DR (2011) 4-Hydroxynonenal inhibits SIRT3 via thiol-specific modification. Chem Res Toxicol 24(5):651–662PubMedCentralPubMedGoogle Scholar
  123. 123.
    Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ (2012) Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One 7(7):e42357PubMedCentralPubMedGoogle Scholar
  124. 124.
    Linnane AW, Eastwood H (2006) Cellular redox regulation and prooxidant signaling systems: a new perspective on the free radical theory of aging. Ann N Y Acad Sci 1067:47–55PubMedGoogle Scholar
  125. 125.
    Linnane AW, Eastwood H (2004) Cellular redox poise modulation; the role of coenzyme Q10, gene and metabolic regulation. Mitochondrion 4(5–6):779–789PubMedGoogle Scholar
  126. 126.
    Linnane AW (2002) Cellular coenzyme Q10 redox poise constitutes a major cell metabolic and gene regulatory system. Biogerontology 3(1–2):3–6PubMedGoogle Scholar
  127. 127.
    Rusnak F, Reiter T (2000) Sensing electrons: protein phosphatase redox regulation. Trends Biochem Sci 25(11):527–529PubMedGoogle Scholar
  128. 128.
    Echtay KS, Winkler E, Klingenberg M (2000) Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature 408(6812):609–613PubMedGoogle Scholar
  129. 129.
    Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker N (2004) Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37(6):755–767PubMedGoogle Scholar
  130. 130.
    Brand MD, Chien LF, Ainscow EK, Rolfe DF, Porter RK (1994) The causes and functions of mitochondrial proton leak. Biochim Biophys Acta 1187(2):132–139PubMedGoogle Scholar
  131. 131.
    Brand MD, Brindle KM, Buckingham JA, Harper JA, Rolfe DF, Stuart JA (1999) The significance and mechanism of mitochondrial proton conductance. Int J Obes Relat Metab Disord 23(Suppl 6):S4–S11PubMedGoogle Scholar
  132. 132.
    Brown GC, Brand MD (1991) On the nature of the mitochondrial proton leak. Biochim Biophys Acta 1059(1):55–62PubMedGoogle Scholar
  133. 133.
    Porter RK, Brand MD (1995) Causes of differences in respiration rate of hepatocytes from mammals of different body mass. Am J Physiol 269(5 Pt 2):R1213–R1224PubMedGoogle Scholar
  134. 134.
    Rolfe DF, Newman JM, Buckingham JA, Clark MG, Brand MD (1999) Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR. Am J Physiol 276(3 Pt 1):C692–C699PubMedGoogle Scholar
  135. 135.
    Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53(Suppl 1):S130–S135PubMedGoogle Scholar
  136. 136.
    Emre Y, Hurtaud C, Karaca M, Nubel T, Zavala F, Ricquier D (2007) Role of uncoupling protein UCP2 in cell-mediated immunity: how macrophage-mediated insulitis is accelerated in a model of autoimmune diabetes. Proc Natl Acad Sci U S A 104(48):19085–19090PubMedCentralPubMedGoogle Scholar
  137. 137.
    Blanc J, Alves-Guerra MC, Esposito B, Rousset S, Gourdy P, Ricquier D, Tedgui A, Miroux B, Mallat Z (2003) Protective role of uncoupling protein 2 in atherosclerosis. Circulation 107(3):388–390PubMedGoogle Scholar
  138. 138.
    Paradis E, Clavel S, Bouillaud F, Ricquier D, Richard D (2003) Uncoupling protein 2: a novel player in neuroprotection. Trends Mol Med 9(12):522–525PubMedGoogle Scholar
  139. 139.
    Diao J, Allister EM, Koshkin V, Lee SC, Bhattacharjee A, Tang C, Giacca A, Chan CB, Wheeler MB (2008) UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival. Proc Natl Acad Sci U S A 105(33):12057–12062PubMedCentralPubMedGoogle Scholar
  140. 140.
    Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, Miroux B, Couplan E, Alves-Guerra MC, Goubern M, Surwit R, Bouillaud F, Richard D, Collins S, Ricquier D (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26(4):435–439PubMedGoogle Scholar
  141. 141.
    Rousset S, Emre Y, Join-Lambert O, Hurtaud C, Ricquier D, Cassard-Doulcier AM (2006) The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine 35(3–4):135–142PubMedGoogle Scholar
  142. 142.
    Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB (2007) Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449(7159):228–232PubMedGoogle Scholar
  143. 143.
    Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig AJ, Boss O, Kim YB, Zheng XX, Wheeler MB, Shulman GI, Chan CB, Lowell BB (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105(6):745–755PubMedGoogle Scholar
  144. 144.
    Newell MK, Villalobos-Menuey E, Schweitzer SC, Harper ME, Camley RE (2006) Cellular metabolism as a basis for immune privilege. J Immune Based Ther Vaccines 4:1PubMedCentralPubMedGoogle Scholar
  145. 145.
    Harper ME, Antoniou A, Villalobos-Menuey E, Russo A, Trauger R, Vendemelio M, George A, Bartholomew R, Carlo D, Shaikh A, Kupperman J, Newell EW, Bespalov IA, Wallace SS, Liu Y, Rogers JR, Gibbs GL, Leahy JL, Camley RE, Melamede R, Newell MK (2002) Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J 16(12):1550–1557PubMedGoogle Scholar
  146. 146.
    Talbot DA, Hanuise N, Rey B, Rouanet JL, Duchamp C, Brand MD (2003) Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus). Biochem Biophys Res Commun 312(4):983–1038PubMedGoogle Scholar
  147. 147.
    Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415(6867):96–99PubMedGoogle Scholar
  148. 148.
    Murphy MP, Echtay KS, Blaikie FH, Asin-Cayuela J, Cocheme HM, Green K, Buckingham JA, Taylor ER, Hurrell F, Hughes G, Miwa S, Cooper CE, Svistunenko DA, Smith RA, Brand MD (2003) Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from alpha-phenyl-N-tert-butylnitrone. J Biol Chem 278(49):48534–48545PubMedGoogle Scholar
  149. 149.
    Barreiro E, Garcia-Martínez C, Mas S, Ametller E, Gea J, Argilés JM, Busquets S, López-Soriano FJ (2009) UCP3 overexpression neutralizes oxidative stress rather than nitrosative stress in mouse myotubes. FEBS Lett 583(2):350–356PubMedGoogle Scholar
  150. 150.
    Jiang N, Zhang G, Bo H, Qu J, Ma G, Cao D, Wen L, Liu S, Ji LL, Zhang Y (2009) Upregulation of uncoupling protein-3 in skeletal muscle during exercise: a potential antioxidant function. Free Radic Biol Med 46(2):138–145PubMedGoogle Scholar
  151. 151.
    Bezaire V, Spriet LL, Campbell S, Sabet N, Gerrits M, Bonen A, Harper ME (2005) Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation. FASEB J 19(8):977–979PubMedGoogle Scholar
  152. 152.
    Himms-Hagen J, Harper ME (2001) Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: an hypothesis. Exp Biol Med (Maywood) 226(2):78–84Google Scholar
  153. 153.
    Schrauwen P, Hoeks J, Hesselink MK (2006) Putative function and physiological relevance of the mitochondrial uncoupling protein-3: involvement in fatty acid metabolism? Prog Lipid Res 45(1):17–41PubMedGoogle Scholar
  154. 154.
    Mattson MP, Kroemer G (2003) Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol Med 9(5):196–205PubMedGoogle Scholar
  155. 155.
    Mattson MP, Liu D (2003) Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Biochem Biophys Res Commun 304(3):539–549PubMedGoogle Scholar
  156. 156.
    Erlanson-Albertsson C (2003) The role of uncoupling proteins in the regulation of metabolism. Acta Physiol Scand 178(4):405–412PubMedGoogle Scholar
  157. 157.
    Parker N, Affourtit C, Vidal-Puig A, Brand MD (2008) Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria. Biochem J 412(1):131–139PubMedCentralPubMedGoogle Scholar
  158. 158.
    Echtay KS, Esteves TC, Pakay JL, Jekabsons MB, Lambert AJ, Portero-Otín M, Pamplona R, Vidal-Puig AJ, Wang S, Roebuck SJ, Brand MD (2003) A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J 22(16):4103–4110PubMedGoogle Scholar
  159. 159.
    Esteves TC, Parker N, Brand MD (2006) Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria. Biochem J 395(3):619–628PubMedGoogle Scholar
  160. 160.
    Li LX, Skorpen F, Egeberg K, Jørgensen IH, Grill V (2001) Uncoupling protein-2 participates in cellular defense against oxidative stress in clonal beta-cells. Biochem Biophys Res Commun 282(1):273–277PubMedGoogle Scholar
  161. 161.
    Giardina TM, Steer JH, Lo SZ, Joyce DA (2008) Uncoupling protein-2 accumulates rapidly in the inner mitochondrial membrane during mitochondrial reactive oxygen stress in macrophages. Biochim Biophys Acta 1777(2):118–129PubMedGoogle Scholar
  162. 162.
    Mehta SL, Li PA (2009) Neuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke. J Cereb Blood Flow Metab 29(6):1069–1078PubMedGoogle Scholar
  163. 163.
    Echtay KS, Winkler E, Frischmuth K, Klingenberg M (2001) Uncoupling proteins 2 and 3 are highly active H(+) transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Proc Natl Acad Sci U S A 98(4):1416–1421PubMedCentralPubMedGoogle Scholar
  164. 164.
    Horvath TL, Diano S, Leranth C, Garcia-Segura LM, Cowley MA, Shanabrough M, Elsworth JD, Sotonyi P, Roth RH, Dietrich EH, Matthews RT, Barnstable CJ, Redmond DE Jr (2003) Coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell loss in a primate model of Parkinson's disease. Endocrinology 144(7):2757–2760PubMedGoogle Scholar
  165. 165.
    Reznick RM, Shulman GI (2006) The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol 574:33–39PubMedGoogle Scholar
  166. 166.
    Garesse R, Vallejo CG (2001) Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene 263(1–2):1–16PubMedGoogle Scholar
  167. 167.
    Finck BN, Kelly DP (2007) Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation 115(19):2540–2548PubMedGoogle Scholar
  168. 168.
    Ryan MT, Hoogenraad NJ (2007) Mitochondrial-nuclear communications. Annu Rev Biochem 76:701–722PubMedGoogle Scholar
  169. 169.
    Wagner AE, Ernst IM, Birringer M, Sancak O, Barella L, Rimbach G (2012) A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid Med Cell Longev 2012:835970PubMedCentralPubMedGoogle Scholar
  170. 170.
    Choi HK, Pokharel YR, Lim SC, Han HK, Ryu CS, Kim SK, Kwak MK, Kang KW (2009) Inhibition of liver fibrosis by solubilized coenzyme Q10: role of Nrf2 activation in inhibiting transforming growth factor-β1 expression. Toxicol Appl Pharmacol 240(3):377–384PubMedGoogle Scholar
  171. 171.
    Garnier A, Fortin D, Zoll J, N'Guessan B, Mettauer B, Lampert E, Veksler V, Ventura-Clapier R (2005) Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle. FASEB J 19(1):43–52PubMedGoogle Scholar
  172. 172.
    Hood DA (2001) Invited review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90(3):1137–1157PubMedGoogle Scholar
  173. 173.
    Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1(6):361–370PubMedGoogle Scholar
  174. 174.
    Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88(2):611–638PubMedGoogle Scholar
  175. 175.
    Hood DA, Adhihetty PJ, Colavecchia M, Gordon JW, Irrcher I, Joseph AM, Lowe ST, Rungi AA (2003) Mitochondrial biogenesis and the role of the protein import pathway. Med Sci Sports Exerc 35(1):86–94PubMedGoogle Scholar
  176. 176.
    Bereiter-Hahn J (1990) Behavior of mitochondria in the living cell. Int Rev Cytol 122:1–63PubMedGoogle Scholar
  177. 177.
    Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24(1):78–90PubMedGoogle Scholar
  178. 178.
    Wu Z, Boss O (2007) Targeting PGC-1 alpha to control energy homeostasis. Expert Opin Ther Targets 11(10):1329–1338PubMedGoogle Scholar
  179. 179.
    Cantó C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20(2):98–105PubMedCentralPubMedGoogle Scholar
  180. 180.
    Liang H, Ward WF (2006) PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ 30(4):145–151PubMedGoogle Scholar
  181. 181.
    Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576(1–2):1–14PubMedGoogle Scholar
  182. 182.
    Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18(4):357–368PubMedGoogle Scholar
  183. 183.
    Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 1813(7):1269–1278PubMedCentralPubMedGoogle Scholar
  184. 184.
    Yang YM, Noh K, Han CY, Kim SG (2010) Transactivation of genes encoding for phase II enzymes and phase III transporters by phytochemical antioxidants. Molecules 15(9):6332–6348. doi: 10.3390/molecules15096332 PubMedGoogle Scholar
  185. 185.
    Lee DH, Gold R, Linker RA (2012) Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: therapeutic modulation via fumaric acid esters. Int J Mol Sci 13(9):11783–11803PubMedCentralPubMedGoogle Scholar
  186. 186.
    Hahm KB, Lee HJ, Han Y, Kim EH, Kim YJ (2012) A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats. BMC Gastroenterol 12(1):143PubMedCentralPubMedGoogle Scholar
  187. 187.
    Reichard JF, Motz GT, Puga A (2007) Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res 35(21):7074–7086PubMedCentralPubMedGoogle Scholar
  188. 188.
    Zhu H, Itoh K, Yamamoto M, Zweier JL, Li Y (2005) Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury. FEBS Lett 579(14):3029–3036PubMedGoogle Scholar
  189. 189.
    Dreger H, Westphal K, Weller A, Baumann G, Stangl V, Meiners S, Stangl K (2009) Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res 83(2):354–361PubMedGoogle Scholar
  190. 190.
    Schmelzer C, Niklowitz P, Okun JG, Haas D, Menke T, Döring F (2011) Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans. IUBMB Life 63(1):42–48PubMedGoogle Scholar
  191. 191.
    Moon HJ, Ko WK, Han SW, Kim DS, Hwang YS, Park HK, Kwon IK (2012) Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation. Biochem Biophys Res Commun 418(2):247–253PubMedGoogle Scholar
  192. 192.
    Kandhare AD, Ghosh P, Ghule AE, Bodhankar SL (2012) Elucidation of molecular mechanism involved in neuroprotective effect of coenzyme Q10 in alcohol-induced neuropathic pain. Fundam Clin Pharmacol. doi: 10.1111/fcp.12003 PubMedGoogle Scholar
  193. 193.
    Bliznakov E, Casey A, Premuzic E (1970) Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26(9):253–254Google Scholar
  194. 194.
    Kawase I, Niitani H, Saijo N, Sasaki H, Morita T (1978) Enhancing effect of coenzyme Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69(4):493–497PubMedGoogle Scholar
  195. 195.
    Folkers K, Shizukuishi S, Takemura K, Drzewoski J, Richardson P, Ellis J, Kuzell WC (1982) Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38(2):335–338PubMedGoogle Scholar
  196. 196.
    Folkers K, Hanioka T, Xia LJ, McRee JT Jr, Langsjoen P (1991) Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176(2):786–791PubMedGoogle Scholar
  197. 197.
    Barbieri B, Lund B, Lundström B, Scaglione F (1999) Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers—a single blind placebo-controlled and randomized clinical study. Biofactors 9(2–4):351–357PubMedGoogle Scholar
  198. 198.
    Bliznakov EG (1973) Effect of stimulation of the host defense system by coenzyme Q10 on dibenzpyrene-induced tumors and infection with friend leukemia virus in mice. Proc Natl Acad Sci U S A 70(2):390–394PubMedCentralPubMedGoogle Scholar
  199. 199.
    Bliznakov EG (1977) Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y (eds) Biomedical and clinical aspects of coenzyme Q. Elsevier, Amsterdam, The Netherlands, pp 73–83Google Scholar
  200. 200.
    Bliznakov EG, Adler AD (1972) Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38(6):393–410Google Scholar
  201. 201.
    Villalba JM, Crane FL, Navas P (1998) Plasma membrane redox system and their role in biological stress and disease. In: Asard H, Berczi A, Caubergs RJ (eds) Kluwer, Dordrecht, vol 1, Vol., pp 247–265Google Scholar
  202. 202.
    Navas P, Fernandez-Ayala DM, Martin SF, Lopez-Lluch G, De Caboa R, Rodriguez-Aguilera JC, Villalba JM (2002) Ceramide-dependent caspase 3 activation is prevented by coenzyme Q from plasma membrane in serum-deprived cells. Free Radic Res 36(4):369–374PubMedGoogle Scholar
  203. 203.
    Fontaine E, Eriksson O, Ichas F, Bernardi P (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation by electron flow through the respiratory chain complex i. J Biol Chem 273(20):12662–12668PubMedGoogle Scholar
  204. 204.
    Wolf BB, Green DR (1999) Suicidal tendencies: apoptotic cell death by caspase family proteinases. J Biol Chem 274(29):20049–20052PubMedGoogle Scholar
  205. 205.
    Maes M, Mihaylova I, Leunis JC (2006) Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett 27(5):615–621PubMedGoogle Scholar
  206. 206.
    Manuel y Keenoy B, Moorkens G, Vertommen J, De Leeuw I (2001) Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci 68(17):2037–2049PubMedGoogle Scholar
  207. 207.
    Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA (2003) Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett 335(3):151–154PubMedGoogle Scholar
  208. 208.
    Smirnova IV, Pall ML (2003) Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Mol Cell Biochem 248(1–2):93–95PubMedGoogle Scholar
  209. 209.
    Miwa K, Fujita M (2009) Increased oxidative stress suggested by low serum vitamin E concentrations in patients with chronic fatigue syndrome. Int J Cardiol 136(2):238–239PubMedGoogle Scholar
  210. 210.
    Jason L, Sorenson M, Sebally K, Alkazemi D, Lerch A, Porter N, Kubow S (2011) Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome. Brain Behav Immun 25(8):1544–1554PubMedGoogle Scholar
  211. 211.
    Brkic S, Tomic S, Maric D, Novakov Mikic A, Turkulov V (2010) Lipid peroxidation is elevated in female patients with chronic fatigue syndrome. Med Sci Monit 16(12):CR628–CR632PubMedGoogle Scholar
  212. 212.
    Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ (2005) Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic Biol Med 39(5):584–589PubMedGoogle Scholar
  213. 213.
    Manuel y Keenoy B, Moorkens G, Vertommen J, Noe M, Neve J, De Leeuw I (2000) Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr 19(3):374–382PubMedGoogle Scholar
  214. 214.
    Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL (2000) Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 5(1):35–41PubMedGoogle Scholar
  215. 215.
    Richards RS, Wang L, Jelinek H (2007) Erythrocyte oxidative damage in chronic fatigue syndrome. Arch Med Res 38(1):94–98PubMedGoogle Scholar
  216. 216.
    Miwa K, Fujita M (2010) Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels 25(4):319–323PubMedGoogle Scholar
  217. 217.
    Maes M, Mihaylova I, Kubera M, Bosmans E (2007) Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome. Neuro Endocrinol Lett 28(4):463–469PubMedGoogle Scholar
  218. 218.
    Maes M, Twisk FNM, Kubera M, Ringel K (2012) Evidence for inflammation and activation of cell-mediated immunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord 136(3):933–939PubMedGoogle Scholar
  219. 219.
    Jammes Y, Steinberg JG, Mambrini O, Bregeon F, Delliaux S (2005) Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med 257(3):299–310PubMedGoogle Scholar
  220. 220.
    Jammes Y, Steinberg JG, Delliaux S, Bregeon F (2009) Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med 266(2):196–206PubMedGoogle Scholar
  221. 221.
    Jammes Y, Steinberg JG, Delliaux S (2011) Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 272(1):74–84Google Scholar
  222. 222.
    Fulle S, Pietrangelo T, Mancinelli R, Saggini R, Fano G (2007) Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis. J Muscle Res Cell Motil 28(6):355–362PubMedGoogle Scholar
  223. 223.
    Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ (2012) Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed 25(9):1073–1087PubMedGoogle Scholar
  224. 224.
    Maes M, Mihaylova I, Leunis JC (2007) Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression. Neuro Endocrinol Lett 28(6):861–867PubMedGoogle Scholar
  225. 225.
    Nathan N, Van Konynenburg RA (2009) Treatment study of methylation cycle support in patients with chronic fatigue syndrome and fibromyalgia. 9th International IACFS/ME Conference, Reno, NevadaGoogle Scholar
  226. 226.
    Morris G, Maes M (2012) A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis. doi: 10.1007/s11011-012-9324-8
  227. 227.
    Morris G, Maes M (2012) Increased nuclear factor-κB and loss of p53 are key mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Hypotheses 79(5):607–613. doi: 10.1016/j.mehy.2012.07.034 PubMedGoogle Scholar
  228. 228.
    Vermeulen RC, Kurk RM, Visser FC, Sluiter W, Scholte HR (2010) Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med 8:93. doi: 10.1186/1479-5876-8-93 PubMedCentralPubMedGoogle Scholar
  229. 229.
    Paul L, Wood L, Behan WM, Maclaren WM (1999) Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol 6(1):63–69PubMedGoogle Scholar
  230. 230.
    Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ (1984) Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1(8391):1367–1369PubMedGoogle Scholar
  231. 231.
    Behan WM, More IA, Behan PO (1991) Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol 83(1):61–65PubMedGoogle Scholar
  232. 232.
    Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R (1998) Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord 8(3–4):204–209PubMedGoogle Scholar
  233. 233.
    Plioplys AV, Plioplys S (1995) Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology 32(4):175–181PubMedGoogle Scholar
  234. 234.
    Lane RJM, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC (1998) Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 64(3):362–367PubMedGoogle Scholar
  235. 235.
    Allen DG, Lamb GD, Westerbland H (2008) Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 88(1):287–332PubMedGoogle Scholar
  236. 236.
    Wu I-C, Ohsawa I, Fuku N, Tanaka M (2010) Metabolic analysis of 13C-labeled pyruvate for noninvasive assessment of mitochondrial function. Ann NY Acad Sci 1201:111–120PubMedGoogle Scholar
  237. 237.
    Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C, Falasca AI, Formiggini G, Castelli GP, Lenaz G (2004) The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann NY Acad Sci 1011:86–100PubMedGoogle Scholar
  238. 238.
    Ozgocmen S, Ozyurt H, Sogut S, Akyol O, Ardicoglu O, Yildizhan H (2006) Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns. Rheumatol Int 26(7):598–603PubMedGoogle Scholar
  239. 239.
    Altindag O, Celik H (2006) Total antioxidant capacity and the severity of the pain in patients with fibromyalgia. Redox Rep 11(3):131–135PubMedGoogle Scholar
  240. 240.
    Sendur OF, Turan Y, Tastaban E, Yenisey C, Serter M (2009) Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study. Rheumatol Int 29(6):629–633PubMedGoogle Scholar
  241. 241.
    Cordero MD (2011) Oxidative stress in fibromyalgia: pathophysiology and clinical implications. Reumatol Clin 7(5):281–283PubMedGoogle Scholar
  242. 242.
    Neyal M, Yimenicioglu F, Aydeniz A, Taskin A, Saglam S, Cekmen M, Neyal A, Gursoy S, Erel O, Balat A (2012) Plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in patients with tension-type headache and fibromyalgia. Clin Neurol Neurosurg S0303–8467(12):00453, 2Google Scholar
  243. 243.
    Cordero MD, Moreno-Fernández AM, Carmona-López MI, Sánchez-Alcázar JA, Rodríguez AF, Navas P, de Miguel M (2010) Mitochondrial dysfunction in skin biopsies and blood mononuclear cells from two cases of fibromyalgia patients. Clin Biochem 43(13–14):1174–1176PubMedGoogle Scholar
  244. 244.
    Cordero MD, de Miguel M, Moreno-Fernández AM (2011) Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease. Med Clin (Barc) 136(6):252–256Google Scholar
  245. 245.
    Moylan S, Maes M, Wray NR, Berk M (2012) The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry. doi: 10.1038/mp.2012.33 PubMedGoogle Scholar
  246. 246.
    Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36(2):764–785PubMedGoogle Scholar
  247. 247.
    Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 35(3):676–692PubMedGoogle Scholar
  248. 248.
    Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G (2012) Antioxidants as antidepressants: fact or fiction? CNS Drugs 26(6):477–490PubMedGoogle Scholar
  249. 249.
    Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52(2):381–389PubMedGoogle Scholar
  250. 250.
    Floor E, Wetzel MG (1998) Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 70(1):268–275PubMedGoogle Scholar
  251. 251.
    Good PF, Hsu A, Werner P, Perl DP, Olanow CW (1998) Protein nitration in Parkinson’s disease. J Neuropathol Exp Neurol 57(4):338–342PubMedGoogle Scholar
  252. 252.
    Dexter D, Carter C, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1986) Lipid peroxidation as cause of nigral cell death in Parkinson’s disease. Lancet 2(8507):639–640PubMedGoogle Scholar
  253. 253.
    Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, Marsischky G, Kolodner RD, Labaer J, Rochet JC, Bonini NM, Lindquist S (2006) Alpha-synuclein blocks ER–Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313(5785):324–328PubMedCentralPubMedGoogle Scholar
  254. 254.
    Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345(1–2):91–104PubMedGoogle Scholar
  255. 255.
    Dexter DT, Holley AE, Flitter WD, Slater TF, Wells FR, Daniel SE, Lees AJ, Jenner P, Marsden CD (1994) Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 9(1):92–97PubMedGoogle Scholar
  256. 256.
    Kirches E (2009) Do mtDNA mutations participate in the pathogenesis of sporadic Parkinson’s disease? Curr Genomics 10(8):585–593PubMedGoogle Scholar
  257. 257.
    Thomas B, Beal MF (2007) Parkinson’s disease. Hum Mol Genet 16(2):R183–R194PubMedGoogle Scholar
  258. 258.
    Schapira AH (2007) Mitochondrial dysfunction in Parkinson’s disease. Cell Death Differ 14(7):1261–1266PubMedGoogle Scholar
  259. 259.
    Chinta SJ, Andersen JK (2008) Redox imbalance in Parkinson’s disease. Biochim Biophys Acta 1780(11):1362–1367PubMedCentralPubMedGoogle Scholar
  260. 260.
    Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa Y (1989) Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun 163(3):1450–1455PubMedGoogle Scholar
  261. 261.
    Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (1989) Mitochondrial complex I deficiency in Parkinson’s disease. Lancet 1(8649):1269PubMedGoogle Scholar
  262. 262.
    Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827PubMedGoogle Scholar
  263. 263.
    Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD (1990) Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 55(6):2142–2145PubMedGoogle Scholar
  264. 264.
    Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26(19):5256–5264PubMedGoogle Scholar
  265. 265.
    Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 4(1):27–34PubMedGoogle Scholar
  266. 266.
    Parker WD Jr, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26(6):719–723PubMedGoogle Scholar
  267. 267.
    Shoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC (1991) Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann Neurol 30(3):332–339PubMedGoogle Scholar
  268. 268.
    Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grünblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wüllner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR, Global PD Gene Expression (GPEX) Consortium (2010) PGC-1α, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med 2(52):52ra73PubMedCentralPubMedGoogle Scholar
  269. 269.
    Cheung ZH, Ip NY (2009) The emerging role of autophagy in Parkinson’s disease. Mol Brain 2:29PubMedCentralPubMedGoogle Scholar
  270. 270.
    Ahmed I, Liang Y, Schools S, Dawson VL, Dawson TM, Savitt JM (2012) Development and characterization of a new Parkinson’s disease model resulting from impaired autophagy. J Neurosci 32(46):16503–16509PubMedCentralPubMedGoogle Scholar
  271. 271.
    Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O'Kane CJ, Rubinsztein DC (2011) Complex inhibitory effects of nitric oxide on autophagy. Mol Cell 43(1):19–32PubMedCentralPubMedGoogle Scholar
  272. 272.
    Sevcsik E, Trexler AJ, Dunn JM, Rhoades E (2011) Allostery in a disordered protein: oxidative modifications to α-synuclein act distally to regulate membrane binding. J Am Chem Soc 133(18):7152–7158PubMedCentralPubMedGoogle Scholar
  273. 273.
    Uversky VN, Yamin G, Munishkina LA, Karymov MA, Millett IS, Doniach S, Lyubchenko YL, Fink AL (2005) Effects of nitration on the structure and aggregation of alpha-synuclein. Brain Res Mol Brain Res 134(1):84–102PubMedGoogle Scholar
  274. 274.
    Protter D, Lang C, Cooper AA (2012) α-Synuclein and mitochondrial dysfunction: a pathogenic partnership in Parkinson’s disease? Park Dis 2012:829207Google Scholar
  275. 275.
    Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889PubMedGoogle Scholar
  276. 276.
    Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884PubMedGoogle Scholar
  277. 277.
    Sánchez-Pérez AM, Claramonte-Clausell B, Sánchez-Andrés JV, Herrero MT (2012) Parkinson’s disease and autophagy. Park Dis 2012:429524Google Scholar
  278. 278.
    Mitra S, Tsvetkov AS, Finkbeiner S (2009) Protein turnover and inclusion body formation. Autophagy 5(7):1037–1038PubMedCentralPubMedGoogle Scholar
  279. 279.
    Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451(7182):1069–1075PubMedCentralPubMedGoogle Scholar
  280. 280.
    Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12(2):119–131PubMedGoogle Scholar
  281. 281.
    Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8(1):e1000298PubMedCentralPubMedGoogle Scholar
  282. 282.
    Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrané J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 107(1):378–383PubMedCentralPubMedGoogle Scholar
  283. 283.
    Maes M, Twisk FN (2009) Chronic fatigue syndrome: la bête noire of the Belgian Health Care System. Neuro Endocrinol Lett 30(3):300–311PubMedGoogle Scholar
  284. 284.
    Cordero MD, Alcocer-Gómez E, de Miguel M, Cano-García FJ, Luque CM, Fernández-Riejo P, Fernández AM, Sánchez-Alcazar JA (2011) Coenzyme Q(10): a novel therapeutic approach for fibromyalgia? Case series with 5 patients. Mitochondrion 11(4):623–625PubMedGoogle Scholar
  285. 285.
    Miyamae T, Seki M, Naga T, Uchino S, Asazuma H, Yoshida T, Iizuka Y, Kikuchi M, Imagawa T, Natsumeda Y, Yokota S, Yamamoto Y (2013) Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation. Redox Rep 18(1):12–19PubMedGoogle Scholar
  286. 286.
    Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA (2005) Treatment of statin adverse effects with supplemental coenzyme Q10 and statin drug discontinuation. Biofactors 25(1–4):147–152PubMedGoogle Scholar
  287. 287.
    Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP (2003) Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 18(1–4):113–124PubMedGoogle Scholar
  288. 288.
    Lamperti C, Naini AB, Lucchini V, Prelle A, Bresolin N, Moggio M, Sciacco M, Kaufmann P, DiMauro S (2005) Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol 62(11):1709–1712PubMedGoogle Scholar
  289. 289.
    Päivä H, Thelen KM, Van Coster R, Smet J, De Paepe B, Mattila KM, Laakso J, Lehtimäki T, von Bergmann K, Lütjohann D, Laaksonen R (2005) High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther 78(1):60–68PubMedGoogle Scholar
  290. 290.
    Mabuchi H, Higashikata T, Kawashiri M, Katsuda S, Mizuno M, Nohara A, Inazu A, Koizumi J, Kobayashi J (2005) Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb 12(2):111–119PubMedGoogle Scholar
  291. 291.
    Chu CS, Kou HS, Lee CJ, Lee KT, Chen SH, Voon WC, Sheu SH, Lai WT (2006) Effect of atorvastatin withdrawal on circulating coenzyme Q10 concentration in patients with hypercholesterolemia. Biofactors 28(3–4):177–184PubMedGoogle Scholar
  292. 292.
    Butler MG, Dasouki M, Bittel D, Hunter S, Naini A, DiMauro S (2003) Coenzyme Q10 levels in Prader–Willi syndrome: comparison with obese and non-obese subjects. Am J Med Genet A 119A(2):168–171PubMedGoogle Scholar
  293. 293.
    Cooper JM, Korlipara LV, Hart PE, Bradley JL, Schapira AH (2008) Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy. Eur J Neurol 15(12):1371–1379PubMedGoogle Scholar
  294. 294.
    Siciliano G, Mancuso M, Tedeschi D, Manca ML, Renna MR, Lombardi V, Rocchi A, Martelli F, Murri L (2001) Coenzyme Q10, exercise lactate and CTG trinucleotide expansion in myotonic dystrophy. Brain Res Bull 56(3–4):405–410PubMedGoogle Scholar
  295. 295.
    Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009) Lower plasma coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocrinol Lett 30(4):462–469PubMedGoogle Scholar
  296. 296.
    Moreno-Fernández AM, Cordero MD, Garrido-Maraver J, Alcocer-Gómez E, Casas-Barquero N, Carmona-López MI, Sánchez-Alcázar JA, de Miguel M (2012) Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients. J Psychiatr Res 46(3):341–345PubMedGoogle Scholar
  297. 297.
    Matsubara T, Azuma T, Yoshida S, Yamagami T (1991) Serum coenzyme Q-10 level in Parkinson syndrome. In: Folkers K, Littarru P, Yamagami T (eds) Biomedical and clinical aspects of coenzyme Q. Elsevier, Amsterdam, pp 159–166Google Scholar
  298. 298.
    Mizuno K, Tanaka M, Nozaki S, Mizuma H, Ataka S, Tahara T, Sugino T, Shirai T, Kajimoto Y, Kuratsune H, Kajimoto O, Watanabe Y (2008) Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition 24(4):293–299PubMedGoogle Scholar
  299. 299.
    Gökbel H, Gül I, Belviranl M, Okudan N (2010) The effects of coenzyme Q10 supplementation on performance during repeated bouts of supramaximal exercise in sedentary men. J Strength Cond Res 24(1):97–102PubMedGoogle Scholar
  300. 300.
    Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, Rasmussen C, Greenwood M, Leutholtz B, Willoughby D, Kreider R (2008) Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. J Int Soc Sports Nutr 5:8PubMedCentralPubMedGoogle Scholar
  301. 301.
    Díaz-Castro J, Guisado R, Kajarabille N, García C, Guisado IM, de Teresa C, Ochoa JJ (2012) Coenzyme Q(10) supplementation ameliorates inflammatory signaling and oxidative stress associated with strenuous exercise. Eur J Nutr 51(7):791–799PubMedGoogle Scholar
  302. 302.
    Bonakdar RA, Guarneri E (2005) Coenzyme Q10. Am Fam Physician 72(6):1065–1070PubMedGoogle Scholar
  303. 303.
    Singh RB, Neki NS, Kartikey K, Pella D, Kumar A, Niaz MA, Thakur AS (2003) Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem 246(1–2):75–82PubMedGoogle Scholar
  304. 304.
    Caso G, Kelly P, McNurlan MA, Lawson WE (2007) Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. Am J Cardiol 99(10):1409–1412PubMedGoogle Scholar
  305. 305.
    Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, Hohl RJ, Trepel J, Liang B, Patronas N, Venzon DJ, Reed E, Myers CE (1996) Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res 2(3):483–491PubMedGoogle Scholar
  306. 306.
    Kim WS, Kim MM, Choi HJ, Yoon SS, Lee MH, Park K, Park CH, Kang WK (2001) Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest New Drugs 19(1):81–83PubMedGoogle Scholar
  307. 307.
    Fedacko J, Pella D, Fedackova P, Hänninen O, Tuomainen P, Jarcuska P, Lopuchovsky T, Jedlickova L, Merkovska L, Littarru GP (2013) Coenzyme Q10 and selenium in statin-associated myopathy treatment. Can J Physiol Pharmacol 91(2):165–170PubMedGoogle Scholar
  308. 308.
    Lister RE (2002) An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome. J Int Med Res 30(2):195–199PubMedGoogle Scholar
  309. 309.
    Fu X, Ji R, Dam J (2010) Antifatigue effect of coenzyme Q10 in mice. J Med Food 13(1):211–215PubMedGoogle Scholar
  310. 310.
    Cordero MD, Alcocer-Gómez E, de Miguel M, Culic O, Carrión AM, Alvarez-Suarez JM, Bullón P, Battino M, Fernández-Rodríguez A, Sánchez-Alcazar JA (2013) Can coenzyme Q10 improve clinical and molecular parameter in fibromyalgia? Antioxid Redox Signal. doi: 10.1089/ars.2013.5260
  311. 311.
    Barbiroli B, Frassineti C, Martinelli P, Iotti S, Lodi R, Cortelli P, Montagna P (1997) Coenzyme Q10 improves mitochondrial respiration in patients with mitochondrial cytopathies. An in vivo study on brain and skeletal muscle by phosphorous magnetic resonance spectroscopy. Cell Mol Biol 43(5):741–749PubMedGoogle Scholar
  312. 312.
    Bresolin N, Doriguzzi C, Ponzetto C, Angelini C, Moroni I, Castelli E, Cossutta E, Binda A, Gallanti A, Gabellini S, Piccolo G, Martinuzzi A, Ciafaloni E, Arnaudo E, Liciardello L, Carenzi A, Scarlato G (1990) Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J Neurol Sci 100(1–2):70–78PubMedGoogle Scholar
  313. 313.
    Chan A, Reichmann H, Kogel A, Beck A, Gold R (1998) Metabolic changes in patients with mitochondrial myopathies and effects of coenzyme Q10 therapy. J Neurol 245(10):681–685PubMedGoogle Scholar
  314. 314.
    Kwong LK, Kamzalov S, Rebrin I, Bayne AC, Jana CK, Morris P, Forster MJ, Sohal RS (2002) Effects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radic Biol Med 33(5):627–638PubMedGoogle Scholar
  315. 315.
    Kamzalov S, Sumien N, Forster MJ, Sohal RS (2003) Coenzyme Q intake elevates the mitochondrial and tissue levels of coenzyme Q and alpha-tocopherol in young mice. J Nutr 133(10):3175–3180PubMedGoogle Scholar
  316. 316.
    Yamamoto M, Sato T, Anno M, Ujike H, Takemoto M (1987) Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes with recurrent abdominal symptoms and coenzyme Q10 administration. J Neurol Neurosurg Psychiatry 50:1475–1481PubMedGoogle Scholar
  317. 317.
    Ihara Y, Namba R, Kuroda S, Sato T, Shirabe T (1989) Mitochondrial encephalomyopathy (MELAS): pathological study and successful therapy with coenzyme Q10 and idebenone. J Neurol Sci 90(3):263–271PubMedGoogle Scholar
  318. 318.
    Goda S, Hamada T, Ishimoto S, Kobayashi T, Goto I, Kuroiwa Y (1987) Clinical improvement after administration of coenzyme Q10 in a patient with mitochondrial encephalomyopathy. J Neurol 234(1):62–63PubMedGoogle Scholar
  319. 319.
    Abe K, Matsuo Y, Kadekawa J, Inoue S, Yanagihara T (1999) Effect of coenzyme Q10 in patients with mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS): evaluation by noninvasive tissue oximetry. J Neurol Sci 162(1):65–68PubMedGoogle Scholar
  320. 320.
    Bendahan D, Desnuelle C, Vanuxem D, Confort-Gouny S, Figarella-Branger D, Pellissier JF, Kozak-Ribbens G, Pouget J, Serratrice G, Cozzone PJ (1992) 31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies. Neurology 42(6):1203–1208PubMedGoogle Scholar
  321. 321.
    Nishikawa Y, Takahashi M, Yorifuji S, Nakamura Y, Ueno S, Tarui S, Kozuka T, Nishimura T (1989) Longterm coenzyme Q10 therapy for a mitochondrial encephalomyopathy with cytochrome c oxidase deficiency: a 31P NMR study. Neurology 39(3):399–403PubMedGoogle Scholar
  322. 322.
    Folkers K, Simonsen R (1995) Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies. Biochim Biophys Acta 1271(1):281–286PubMedGoogle Scholar
  323. 323.
    Chen RS, Huang CC, Chu NS (1997) Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. Eur Neurol 37(4):212–218PubMedGoogle Scholar
  324. 324.
    Andersen CB, Henriksen JE, Hother-Nielsen O, Vaag A, Mortensen SA, BeckNielsen H (1997) The effect of coenzyme Q10 on blood glucose and insulin requirement in patients with insulin dependent diabetes mellitus. Mol Aspects Med 18(Suppl):S307–S309PubMedGoogle Scholar
  325. 325.
    Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, Weissman BM, Tsao CY, Mendell JR, Shanske S, De Vivo DC, Hirano M, DiMauro S (2001) Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 56(7):849–855PubMedGoogle Scholar
  326. 326.
    Aboul-Fotouh S (2013) Coenzyme Q10 displays antidepressant-like activity with reduction of hippocampal oxidative/nitrosative DNA damage in chronically stressed rats. Pharmacol Biochem Behav 104:105–112PubMedGoogle Scholar
  327. 327.
    Moreno-Fernández AM, Cordero MD, Garrido-Maraver J, Alcocer-Gómez E, Casas-Barquero N, Carmona-López MI, Sánchez-Alcázar JA, de Miguel M (2012) Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients. J Psychiatr Res 46:341–345PubMedGoogle Scholar
  328. 328.
    Chao J, Leung Y, Wang M, Chang RC (2012) Nutraceuticals and their preventive or potential therapeutic value in Parkinson’s disease. Nutr Rev 70(7):373–386PubMedGoogle Scholar
  329. 329.
    Sutachan JJ, Casas Z, Albarracin SL, Stab BR 2nd, Samudio I, Gonzalez J, Morales L, Barreto GE (2012) Cellular and molecular mechanisms of antioxidants in Parkinson’s disease. Nutr Neurosci 15(3):120–126PubMedGoogle Scholar
  330. 330.
    Santos CM (2012) New agents promote neuroprotection in Parkinson’s disease models. CNS Neurol Disord Drug Targets 11(4):410–418PubMedGoogle Scholar
  331. 331.
    Ebadi M, Govitrapong P, Sharma S, Muralikrishnan D, Shavali S, Pellett L, Schafer R, Albano C, Eken J (2001) Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of Parkinson’s disease. Biol Signals Recept 10(3–4):224–253PubMedGoogle Scholar
  332. 332.
    Beal MF, Shults CW (2003) Effects of coenzyme Q10 in Huntington’s disease and early Parkinson’s disease. Biofactors 18(1–4):153–161PubMedGoogle Scholar
  333. 333.
    Gao X, Simon KC, Schwarzschild MA, Ascherio A (2012) Prospective study of statin use and risk of Parkinson disease. Arch Neurol 69(3):380–384PubMedCentralPubMedGoogle Scholar
  334. 334.
    Martín SF, Gómez-Díaz C, Navas P, Villalba JM (2002) Ubiquinol inhibition of neutral sphingomyelinase in liver plasma membrane: specific inhibition of the Mg(2+)-dependent enzyme and role of isoprenoid chain. Biochem Biophys Res Commun 297(3):581–586PubMedGoogle Scholar
  335. 335.
    Yalcin A, Kilinc E, Kocturk S, Resmi H, Sozmen EY (2004) Effect of melatonin cotreatment against kainic acid on coenzyme Q10, lipid peroxidation and Trx mRNA in rat hippocampus. Int J Neurosci 114(9):1085–1097PubMedGoogle Scholar
  336. 336.
    Shults CW (2005) Therapeutic role of coenzyme Q(10) in Parkinson’s disease. Pharmacol Ther 107(1):120–130PubMedGoogle Scholar
  337. 337.
    Shults CW, Flint Beal M, Song D, Fontaine D (2004) Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson’s disease. Exp Neurol 188(2):491–494PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Gerwyn Morris
    • 1
  • George Anderson
    • 2
  • Michael Berk
    • 3
    • 4
    • 5
    • 6
  • Michael Maes
    • 3
    • 7
  1. 1.LlanelliUK
  2. 2.CRC Clinical Research Centre/CommunicationsGlasgowUK
  3. 3.School of MedicineDeakin UniversityGeelongAustralia
  4. 4.Department of PsychiatryUniversity of MelbourneParkvilleAustralia
  5. 5.Orygen Youth Health Research CentreParkvilleAustralia
  6. 6.Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  7. 7.Department of PsychiatryChulalongkorn UniversityBangkokThailand

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