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Coenzyme Q10 Analogues: Comparison
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Please note this is a comparison between Version 2 by Conner Chen and Version 1 by José A Sanchez Alcazar.

Coenzyme Q

10

 (CoQ

10

 or ubiquinone) is a mobile proton and electron carrier of the mitochondrial respiratory chain with antioxidant properties widely used as an antiaging health supplement and to relieve the symptoms of many pathological conditions associated with mitochondrial dysfunction. Even though the hegemony of CoQ

10

 in the context of antioxidant-based treatments is undeniable, the future primacy of this quinone is hindered by the promising features of its numerous analogues. Despite the unimpeachable performance of CoQ

10

 therapies, problems associated with their administration and intraorganismal delivery has led clinicians and scientists to search for alternative derivative molecules. Over the past few years, a wide variety of CoQ

10

 analogues with improved properties have been developed. These analogues conserve the antioxidant features of CoQ

10

 but present upgraded characteristics such as water solubility or enhanced mitochondrial accumulation.

  • coenzyme Q10
  • analogues
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References

  1. Carbone, C.; Pignatello, R.; Musumeci, T.; Puglisi, G. Chemical and technological delivery systems for idebenone: A review of literature production. Expert Opin. Drug Deliv. 2012, 9, 1377–1392.
  2. Meier, T.; Buyse, G. Idebenone: An emerging therapy for Friedreich ataxia. J. Neurol. 2009, 256, 25.
  3. Bhagavan, H.N.; Chopra, R.K. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res. 2006, 40, 445–453.
  4. Di Prospero, N.A.; Sumner, C.J.; Penzak, S.R.; Ravina, B.; Fischbeck, K.H.; Taylor, J.P. Safety, Tolerability, and Pharmacokinetics of High-Dose Idebenone in Patients With Friedreich Ataxia. Arch. Neurol. 2007, 64, 803–808.
  5. Bodmer, M.; Vankan, P.; Dreier, M.; Kutz, K.W.; Drewe, J. Pharmacokinetics and metabolism of idebenone in healthy male subjects. Eur. J. Clin. Pharmacol. 2009, 65, 493.
  6. Giorgio, V.; Schiavone, M.; Galber, C.; Carini, M.; Da Ros, T.; Petronilli, V.; Argenton, F.; Carelli, V.; Lopez, M.J.A.; Salviati, L.; et al. The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects. Biochim. Biophys. Acta Bioenerg. 2018, 1859, 901–908.
  7. Esposti, M.D.; Ngo, A.; Ghelli, A.; Benelli, B.; Carelli, V.; McLennan, H.; Linnane, A.W. The Interaction of Q Analogs, Particularly Hydroxydecyl Benzoquinone (Idebenone), with the Respiratory Complexes of Heart Mitochondria. Arch. Biochem. Biophys. 1996, 330, 395–400.
  8. Fato, R.; Bergamini, C.; Leoni, S.; Lenaz, G. Mitochondrial production of reactive oxygen species: Role of Complex I and quinone analogues. BioFactors 2008, 32, 31–39.
  9. Rauchová, H.; Drahota, Z.; Bergamini, C.; Fato, R.; Lenaz, G. Modification of respiratory-chain enzyme activities in brown adipose tissue mitochondria by idebenone (hydroxydecyl-ubiquinone). J. Bioenerg. Biomembr. 2008, 40, 85–93.
  10. Erb, M.; Hoffmann-Enger, B.; Deppe, H.; Soeberdt, M.; Haefeli, R.H.; Rummey, C.; Feurer, A.; Gueven, N. Features of idebenone and related short-chain quinones that rescue ATP levels under conditions of impaired mitochondrial complex I. PLoS ONE 2012, 7, e36153.
  11. Giorgio, V.; Petronilli, V.; Ghelli, A.; Carelli, V.; Rugolo, M.; Lenaz, G.; Bernardi, P. The effects of idebenone on mitochondrial bioenergetics. Biochim. Biophys. Acta Bioenerg. 2012, 1817, 363–369.
  12. Haefeli, R.H.; Erb, M.; Gemperli, A.C.; Robay, D.; Fruh, I.C.; Anklin, C.; Dallmann, R.; Gueven, N. NQO1-dependent redox cycling of idebenone: Effects on cellular redox potential and energy levels. PLoS ONE 2011, 6, e17963.
  13. James, A.M.; Cochemé, H.M.; Smith, R.A.J.; Murphy, M.P. Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species: Implications for the use of exogenous ubiquinones as therapies and experimental tools. J. Biol. Chem. 2005, 280, 21295–21312.
  14. Rauchova, H.; Vokurkova, M.; Drahota, Z. Idebenone-induced recovery of glycerol-3-phosphate and succinate oxidation inhibited by digitonin. Physiol. Res. 2012, 61, 259–265.
  15. Rodenburg, R.J. Mitochondrial complex I-linked disease. Biochim. Biophys. Acta Bioenerg. 2016, 1857, 938–945.
  16. Lee, S.; Sheck, L.; Crowston, J.G.; Van Bergen, N.J.; O’Neill, E.C.; O’Hare, F.; Kong, Y.X.G.; Chrysostomou, V.; Vincent, A.L.; Trounce, I.A. Impaired Complex-I-Linked Respiration and ATP Synthesis in Primary Open-Angle Glaucoma Patient Lymphoblasts. Investig. Ophthalmol. Vis. Sci. 2012, 53, 2431–2437.
  17. Kernt, M.; Arend, N.; Buerger, A.; Mann, T.; Haritoglou, C.; Ulbig, M.W.; Kampik, A.; Hirneiss, C. Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio. J. Glaucoma 2013, 22, 404–412.
  18. Grieb, P.; Ryba, M.S.; Debicki, G.S.; Gordon-Krajcer, W.; Januszewski, S.; Chrapusta, S.J. Changes in oxidative stress in the rat brain during post-cardiac arrest reperfusion, and the effect of treatment with the free radical scavenger idebenone. Resuscitation 1998, 39, 107–113.
  19. Mordente, A.; Martorana, G.E.; Minotti, G.; Giardina, B. Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone). Chem. Res. Toxicol. 1998, 11, 54–63.
  20. Cardoso, S.M.; Pereira, C.; Oliveira, C.R. Mitochondrial function is differentially affected upon oxidative stress. Free Radic. Biol. Med. 1999, 26, 3–13.
  21. Rustin, P.; von Kleist-Retzow, J.-C.; Chantrel-Groussard, K.; Sidi, D.; Munnich, A.; Rötig, A. Effect of idebenone on cardiomyopathy in Friedreich’s ataxia: A preliminary study. Lancet 1999, 354, 477–479.
  22. Theodorou-Kanakari, A.; Karampitianis, S.; Karageorgou, V.; Kampourelli, E.; Kapasakis, E.; Theodossiadis, P.; Chatziralli, I. Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature. Adv. Ther. 2018, 35, 1510–1518.
  23. Klopstock, T.; Yu-Wai-Man, P.; Dimitriadis, K.; Rouleau, J.; Heck, S.; Bailie, M.; Atawan, A.; Chattopadhyay, S.; Schubert, M.; Garip, A.; et al. A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain 2011, 134, 2677–2686.
  24. Klopstock, T.; Metz, G.; Yu-Wai-Man, P.; Büchner, B.; Gallenmüller, C.; Bailie, M.; Nwali, N.; Griffiths, P.G.; von Livonius, B.; Reznicek, L.; et al. Persistence of the treatment effect of idebenone in Leber’s hereditary optic neuropathy. Brain 2013, 136, e230.
  25. Hausse, A.O.; Aggoun, Y.; Bonnet, D.; Sidi, D.; Munnich, A.; Rötig, A.; Rustin, P. Idebenone and reduced cardiac hypertrophy in Friedreich’s ataxia. Heart 2002, 87, 346–349.
  26. Mariotti, C.; Solari, A.; Torta, D.; Marano, L.; Fiorentini, C.; Di Donato, S. Idebenone treatment in Friedreich patients: One-year-long randomized placebo-controlled trial. Neurology 2003, 60, 1676.
  27. Giovanni, D.S.; Valeria, P.; Bahaa, F.; Majid, A.F. Monitoring cardiac function during idebenone therapy in Friedreich’s ataxia. Curr. Pharm. Des. 2015, 21, 479–483.
  28. Long-Term Safety and Tolerability of Idebenone in Friedreich’s Ataxia Patients (MICONOS Extension). Available online: (accessed on 20 January 2021).
  29. Study to Assess the Safety and Tolerability of Idebenone in the Treatment of Friedreich’s Ataxia Patients. Available online: (accessed on 20 January 2021).
  30. A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich’s Ataxia (FRDA) Patients. Available online: (accessed on 20 January 2021).
  31. Idebenone to Treat Friedreich’s Ataxia. Available online: (accessed on 20 January 2021).
  32. Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD). Available online: (accessed on 20 January 2021).
  33. Long-Term Safety, Tolerability and Efficacy of Idebenone in Duchenne Muscular Dystrophy (DELPHI Extension). Available online: (accessed on 20 January 2021).
  34. A Phase III Double-Blind Study with Idebenone in Patients with Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids. Available online: (accessed on 20 January 2021).
  35. Idebenone for Primary Progressive Multiple Sclerosis. Available online: (accessed on 20 January 2021).
  36. Clinical Trial of Idebenone in Primary Progressive Multiple Sclerosis (IPPoMS). Available online: (accessed on 20 January 2021).
  37. Idebenone Treatment of Early Parkinson’s Diseasesymptoms. Available online: (accessed on 20 January 2021).
  38. Study to Assess Efficacy, Safety and Tolerability of Idebenone in the Treatment of Leber’s Hereditary Optic Neuropathy. Available online: (accessed on 20 January 2021).
  39. Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-Like Episodes. Available online: (accessed on 20 January 2021).
  40. Sugizaki, T.; Tanaka, K.-I.; Asano, T.; Kobayashi, D.; Hino, Y.; Takafuji, A.; Shimoda, M.; Mogushi, K.; Kawahara, M.; Mizushima, T. Idebenone has preventative and therapeutic effects on pulmonary fibrosis via preferential suppression of fibroblast activity. Cell Death Discov. 2019, 5, 146.
  41. Galvin, J.E. Chapter 31-Medical Foods and Dietary Approaches in Cognitive Decline, Mild Cognitive Impairment, and Dementia. In Diet and Nutrition in Dementia and Cognitive Decline; Martin, C.R., Preedy, V.R., Eds.; Academic Press: San Diego, CA, USA, 2015; pp. 343–356.
  42. Ikejiri, Y.; Fau-Ishii, K.M.E.; Fau-Nishimoto, K.I.K.; Fau-Yasuda, M.N.K.; Fau-Sasaki, M.Y.M.; Sasaki, M. Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS. Neurology 1996, 47, 583–585.
  43. Petrov, S.; Shmirova, V.; Kozlova, I.; Antonov, A.A. Application of a idebenone in therapy of glaucoma optic neuropathy. Glaucoma 2007, 6, 29–34.
  44. Orsucci, D.; Fau-Ienco, E.C.M.M.; Fau-LoGerfo, A.I.E.; Fau-Siciliano, G.L.A.; Siciliano, G. Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10 and its analogues. Curr. Med. Chem. 2011, 18, 4053–4064.
  45. Kelso, G.F.; Porteous, C.M.; Coulter, C.V.; Hughes, G.; Porteous, W.K.; Ledgerwood, E.C.; Smith, R.A.J.; Murphy, M.P. Selective Targeting of a Redox-active Ubiquinone to Mitochondria within Cells: Antioxidant and antiapoptotic properties. J. Biol. Chem. 2001, 276, 4588–4596.
  46. Smith, R.A.J.; Porteous, C.M.; Coulter, C.V.; Murphy, M.P. Selective targeting of an antioxidant to mitochondria. Eur. J. Biochem. 1999, 263, 709–716.
  47. Murphy, M.P. Selective targeting of bioactive compounds to mitochondria. Trends Biotechnol. 1997, 15, 326–330.
  48. Magwere, T.; West, M.; Riyahi, K.; Murphy, M.P.; Smith, R.A.J.; Partridge, L. The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech. Ageing Dev. 2006, 127, 356–370.
  49. Smith, R.A.J.; Hartley, R.C.; Cochemé, H.M.; Murphy, M.P. Mitochondrial pharmacology. Trends Pharmacol. Sci. 2012, 33, 341–352.
  50. Koopman, W.J.H.; Verkaart, S.; Visch, H.-J.; van der Westhuizen, F.H.; Murphy, M.P.; van den Heuvel, L.W.P.J.; Smeitink, J.A.M.; Willems, P.H.G.M. Inhibition of complex I of the electron transport chain causes O2−·-mediated mitochondrial outgrowth. Am. J. Physiol. Cell Physiol. 2005, 288, C1440–C1450.
  51. Porteous, C.M.; Logan, A.; Evans, C.; Ledgerwood, E.C.; Menon, D.K.; Aigbirhio, F.; Smith, R.A.J.; Murphy, M.P. Rapid uptake of lipophilic triphenylphosphonium cations by mitochondria in vivo following intravenous injection: Implications for mitochondria-specific therapies and probes. Biochim. Biophys. Acta Gen. Subj. 2010, 1800, 1009–1017.
  52. Junior, R.F.R.; Dabkowski, E.R.; Shekar, K.C.; Connell, K.A.O.; Hecker, P.A.; Murphy, M.P. MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload. Free Radic. Biol. Med. 2018, 117, 18–29.
  53. Matthew, J.R.; Jessica, R.S.-P.; Chelsea, A.C.S.; Nina, Z.B.; Lauren, M.C.; Hannah, L.R.; Kayla, A.; Chonchol, M.W.; Rachel, A.G.-R.; Michael, P.M.; et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension 2018, 71, 1056–1063.
  54. Xiao, L.; Xu, X.; Zhang, F.; Wang, M.; Xu, Y.; Tang, D.; Wang, J.; Qin, Y.; Liu, Y.; Tang, C.; et al. The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol. 2017, 11, 297–311.
  55. Chacko, B.K.; Srivastava, A.; Johnson, M.S.; Benavides, G.A.; Chang, M.J.; Ye, Y.; Jhala, N.; Murphy, M.P.; Kalyanaraman, B.; Darley-Usmar, V.M. Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis. Hepatology 2011, 54, 153–163.
  56. Gane, E.J.; Weilert, F.; Orr, D.W.; Keogh, G.F.; Gibson, M.; Lockhart, M.M.; Frampton, C.M.; Taylor, K.M.; Smith, R.A.J.; Murphy, M.P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010, 30, 1019–1026.
  57. Ghosh, A.; Chandran, K.; Kalivendi, S.V.; Joseph, J.; Antholine, W.E.; Hillard, C.J.; Kanthasamy, A.; Kanthasamy, A.; Kalyanaraman, B. Neuroprotection by a mitochondria-targeted drug in a Parkinson’s disease model. Free Radic. Biol. Med. 2010, 49, 1674–1684.
  58. Ünal, İ.; Çalışkan-Ak, E.; Üstündağ, Ü.V.; Ateş, P.S.; Alturfan, A.A.; Altinoz, M.A.; Elmaci, I.; Emekli-Alturfan, E. Neuroprotective effects of mitoquinone and oleandrin on Parkinson’s disease model in zebrafish. Int. J. Neurosci. 2020, 130, 574–582.
  59. McManus, M.J.; Murphy, M.P.; Franklin, J.L. The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease. J. Neurosci. 2011, 31, 15703.
  60. Ng, L.F.; Gruber, J.; Cheah, I.K.; Goo, C.K.; Cheong, W.F.; Shui, G.; Sit, K.P.; Wenk, M.R.; Halliwell, B. The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radic. Biol. Med. 2014, 71, 390–401.
  61. Pinho, B.R.; Duarte, A.I.; Canas, P.M.; Moreira, P.I.; Murphy, M.P.; Oliveira, J.M.A. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington’s disease mice. Free Radic. Biol. Med. 2020, 146, 372–382.
  62. Miquel, E.; Cassina, A.; Martínez-Palma, L.; Souza, J.M.; Bolatto, C.; Rodríguez-Bottero, S.; Logan, A.; Smith, R.A.J.; Murphy, M.P.; Barbeito, L.; et al. Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis. Free Radic. Biol. Med. 2014, 70, 204–213.
  63. Zhou, J.; Wang, H.; Shen, R.; Fang, J.; Yang, Y.; Dai, W.; Zhu, Y.; Zhou, M. Mitochondrial-targeted antioxidant MitoQ provides neuroprotection and reduces neuronal apoptosis in experimental traumatic brain injury possibly via the Nrf2-ARE pathway. Am. J. Transl. Res. 2018, 10, 1887–1899.
  64. A Trial of MitoQ for the Treatment of People with Parkinson’s Disease. Available online: (accessed on 20 January 2021).
  65. MitoQ for Fatigue in Multiple Sclerosis (MS). Available online: (accessed on 20 January 2021).
  66. MitoQ for Fatigue in Multiple Sclerosis. Available online: (accessed on 20 January 2021).
  67. MitoQ for the Treatment of Metabolic Dysfunction in Asthma. Available online: (accessed on 20 January 2021).
  68. The Efficacy of Oral Mitoquinone (MitoQ) Supplementation for Improving Physiological in Middle-Aged and Older Adults. Available online: (accessed on 20 January 2021).
  69. Trial of MitoQ for Raised Liver Enzymes Due to Hepatitis C. Available online: (accessed on 20 January 2021).
  70. A Study to Compare MitoQ and Placebo to Treat Non-Alcoholic Fatty Liver Disease (NAFLD). Available online: (accessed on 20 January 2021).
  71. Lenaz, G.; Bovina, C.; Castelluccio, C.; Fato, R.; Formiggini, G.; Genova, M.L.; Marchetti, M.; Pich, M.M.; Pallotti, F.; Castelli, G.P.; et al. Mitochondrial complex I defects in aging. Mol. Cell Biochem. 1997, 174, 329–333.
  72. Armstrong, J.S.; Whiteman, M.; Rose, P.; Jones, D.P. The Coenzyme Q10 analog decylubiquinone inhibits the redox-activated mitochondrial permeability transition: Role of mitcohondrial [correction mitochondrial] complex III. J. Biol. Chem. 2003, 278, 49079–49084.
  73. Hano, N.; Nakashima, Y.; Shinzawa-Itoh, K.; Yoshikawa, S. Effect of the side chain structure of coenzyme Q on the steady state kinetics of bovine heart NADH: Coenzyme Q oxidoreductase. J. Bioenerg. Biomembr. 2003, 35, 257–265.
  74. Esposti, M.D.; Ngo, A.; McMullen, G.L.; Ghelli, A.; Sparla, F.; Benelli, B.; Ratta, M.; Linnane, A.W. The specificity of mitochondrial complex I for ubiquinones. Biochem. J. 1996, 313 Pt 1, 327–334.
  75. Telford, J.E.; Kilbride, S.M.; Davey, G.P. Decylubiquinone increases mitochondrial function in synaptosomes. J. Biol. Chem. 2010, 285, 8639–8645.
  76. Schagger, H.; Pfeiffer, K. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J. 2000, 19, 1777–1783.
  77. Acin-Perez, R.; Fernandez-Silva, P.; Peleato, M.L.; Perez-Martos, A.; Enriquez, J.A. Respiratory active mitochondrial supercomplexes. Mol. Cell 2008, 32, 529–539.
  78. Yu-Wai-Man, P.; Soiferman, D.; Moore, D.G.; Burte, F.; Saada, A. Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy. Mitochondrion 2017, 36, 36–42.
  79. Hosni-Ahmed, A.; Sims, M.; Jones, T.S.; Patil, R.; Patil, S.; Abdelsamed, H.; Yates, C.R.; Miller, D.D.; Pfeffer, L.M. EDL-360: A Potential Novel Antiglioma Agent. J. Cancer Sci. Ther. 2014, 6, 370–377.
  80. Jun, D.Y.; Rue, S.W.; Han, K.H.; Taub, D.; Lee, Y.S.; Bae, Y.S.; Kim, Y.H. Mechanism underlying cytotoxicity of thialysine, lysine analog, toward human acute leukemia Jurkat T cells. Biochem. Pharmacol. 2003, 66, 2291–2300.
  81. Cao, J.; Liu, X.; Yang, Y.; Wei, B.; Li, Q.; Mao, G.; He, Y.; Li, Y.; Zheng, L.; Zhang, Q.; et al. Decylubiquinone suppresses breast cancer growth and metastasis by inhibiting angiogenesis via the ROS/p53/ BAI1 signaling pathway. Angiogenesis 2020, 23, 325–338.
  82. Murad, L.B.; Guimaraes, M.R.; Vianna, L.M. Effects of decylubiquinone (coenzyme Q10 analog) supplementation on SHRSP. Biofactors 2007, 30, 13–18.
  83. Chakraborthy, A.; Ramani, P.; Sherlin, H.J.; Premkumar, P.; Natesan, A. Antioxidant and pro-oxidant activity of Vitamin C in oral environment. Indian J. Dent. Res. 2014, 25, 499–504.
  84. Vlachantoni, D.; Bramall, A.N.; Murphy, M.P.; Taylor, R.W.; Shu, X.; Tulloch, B.; Van Veen, T.; Turnbull, D.M.; McInnes, R.R.; Wright, A.F. Evidence of severe mitochondrial oxidative stress and a protective effect of low oxygen in mouse models of inherited photoreceptor degeneration. Hum. Mol. Genet. 2011, 20, 322–335.
  85. Antonenko, Y.N.; Avetisyan, A.V.; Bakeeva, L.E.; Chernyak, B.V.; Chertkov, V.A.; Domnina, L.V.; Ivanova, O.Y.; Izyumov, D.S.; Khailova, L.S.; Klishin, S.S.; et al. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies. Biochemistry (Mosc.) 2008, 73, 1273–1287.
  86. Borisova-Mubarakshina, M.M.; Vetoshkina, D.V.; Ivanov, B.N. Antioxidant and signaling functions of the plastoquinone pool in higher plants. Physiol. Plant 2019, 166, 181–198.
  87. Mubarakshina, M.M.; Ivanov, B.N. The production and scavenging of reactive oxygen species in the plastoquinone pool of chloroplast thylakoid membranes. Physiol. Plant 2010, 140, 103–110.
  88. Szechynska-Hebda, M.; Karpinski, S. Light intensity-dependent retrograde signalling in higher plants. J. Plant Physiol. 2013, 170, 1501–1516.
  89. Pinnola, A. The rise and fall of Light-Harvesting Complex Stress-Related proteins as photoprotection agents during evolution. J. Exp. Bot. 2019, 70, 5527–5535.
  90. Green, D.E. The electromechanochemical model for energy coupling in mitochondria. Biochim. Biophys. Acta 1974, 346, 27–78.
  91. Skulachev, V.P.; Anisimov, V.N.; Antonenko, Y.N.; Bakeeva, L.E.; Chernyak, B.V.; Erichev, V.P.; Filenko, O.F.; Kalinina, N.I.; Kapelko, V.I.; Kolosova, N.G.; et al. An attempt to prevent senescence: A mitochondrial approach. Biochim. Biophys. Acta 2009, 1787, 437–461.
  92. Skulachev, M.V.; Antonenko, Y.N.; Anisimov, V.N.; Chernyak, B.V.; Cherepanov, D.A.; Chistyakov, V.A.; Egorov, M.V.; Kolosova, N.G.; Korshunova, G.A.; Lyamzaev, K.G.; et al. Mitochondrial-targeted plastoquinone derivatives. Effect on senescence and acute age-related pathologies. Curr. Drug Targets 2011, 12, 800–826.
  93. Skulachev, V.P.; Antonenko, Y.N.; Cherepanov, D.A.; Chernyak, B.V.; Izyumov, D.S.; Khailova, L.S.; Klishin, S.S.; Korshunova, G.A.; Lyamzaev, K.G.; Pletjushkina, O.Y.; et al. Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs). Biochim. Biophys. Acta (BBA) Bioenerg. 2010, 1797, 878–889.
  94. Plotnikov, E.Y.; Fau-Jankauskas, S.S.S.D.; Fau-Rokitskaya, T.I.J.S.; Fau-Chupyrkina, A.A.R.T.; Fau-Pevzner, I.B.C.A.; Fau-Zorova, L.D.P.I.; Fau-Isaev, N.K.Z.L.; Fau-Antonenko, Y.N.I.N.; Fau-Skulachev, V.P.A.Y.; Fau-Zorov, D.B.S.V.; et al. Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro- and neuroprotective effects of penetrating cations of the SkQ family. Biochemistry 2012, 77, 1029–1037.
  95. Garlid, K.F.; Nakashima, R.A.; Nakashima, R.A. Studies on the mechanism of uncoupling by amine local anesthetics. Evidence for mitochondrial proton transport mediated by lipophilic ion pairs. J. Biol. Chem. 1983, 258, 7974–7980.
  96. Feniouk, B.A.; Skulachev, V.P. Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants. Curr. Aging Sci. 2017, 10, 41–48.
  97. Skulachev, V.P. A biochemical approach to the problem of aging: “megaproject” on membrane-penetrating ions. The first results and prospects. Biochemistry (Mosc.) 2007, 72, 1385–1396.
  98. Wei, Y.; Troger, A.; Spahiu, V.; Perekhvatova, N.; Skulachev, M.; Petrov, A.; Chernyak, B.; Asbell, P. The Role of SKQ1 (Visomitin) in Inflammation and Wound Healing of the Ocular Surface. Ophthalmol. Ther. 2019, 8, 63–73.
  99. Weniger, M.; Reinelt, L.; Neumann, J.; Holdt, L.; Ilmer, M.; Renz, B.; Hartwig, W.; Werner, J.; Bazhin, A.V.; D’Haese, J.G. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxid. Med. Cell. Longev. 2016, 2016, 4650489.
  100. Demyanenko, I.A.; Zakharova, V.V.; Ilyinskaya, O.P.; Vasilieva, T.V.; Fedorov, A.V.; Manskikh, V.N.; Zinovkin, R.A.; Pletjushkina, O.Y.; Chernyak, B.V.; Skulachev, V.P.; et al. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice. Oxid. Med. Cell. Longev. 2017, 2017, 6408278.
  101. Titova, E.; Shagieva, G.; Ivanova, O.; Domnina, L.; Domninskaya, M.; Strelkova, O.; Khromova, N.; Kopnin, P.; Chernyak, B.; Skulachev, V.; et al. Mitochondria-targeted antioxidant SkQ1 suppresses fibrosarcoma and rhabdomyosarcoma tumour cell growth. Cell Cycle 2018, 17, 1797–1811.
  102. Kolosova, N.G.; Tyumentsev, M.A.; Muraleva, N.A.; Kiseleva, E.; Vitovtov, A.O.; Stefanova, N.A. Antioxidant SkQ1 Alleviates Signs of Alzheimer’s Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration. Curr. Alzheimer Res. 2017, 14, 1283–1292.
  103. Jiang, Y.; Liu, C.; Lei, B.; Xu, X.; Lu, B. Mitochondria-targeted antioxidant SkQ1 improves spermatogenesis in Immp2l mutant mice. Andrologia 2018, 50, e12848.
  104. Bakeeva, L.E. Age-Related Changes in Ultrastructure of Mitochondria. Effect of SkQ1. Biochemistry (Mosc.) 2015, 80, 1582–1588.
  105. Tsybul’ko, E.; Krementsova, A.; Symonenko, A.; Rybina, O.; Roshina, N.; Pasyukova, E. The Mitochondria-Targeted Plastoquinone-Derivative SkQ1 Promotes Health and Increases Drosophila melanogaster Longevity in Various Environments. J. Gerontol. A Biol. Sci. Med. Sci. 2017, 72, 499–508.
  106. Yang, Y.; Karakhanova, S.; Soltek, S.; Werner, J.; Philippov, P.P.; Bazhin, A.V. In vivo immunoregulatory properties of the novel mitochondria-targeted antioxidant SkQ1. Mol. Immunol. 2012, 52, 19–29.
  107. Ahmed, E.; Donovan, T.; Yujiao, L.; Zhang, Q. Mitochondrial Targeted Antioxidant in Cerebral Ischemia. J. Neurol. Neurosci. 2015, 6, 2–17.
  108. Loshchenova, P.S.; Sinitsyna, O.I.; Fedoseeva, L.A.; Stefanova, N.A.; Kolosova, N.G. Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats. Biochemistry (Mosc.) 2015, 80, 596–603.
  109. Gueven, N.; Nadikudi, M.; Daniel, A.; Chhetri, J. Targeting mitochondrial function to treat optic neuropathy. Mitochondrion 2017, 36, 7–14.
  110. Anisimov, V.N.; Egorov, M.V.; Krasilshchikova, M.S.; Lyamzaev, K.G.; Manskikh, V.N.; Moshkin, M.P.; Novikov, E.A.; Popovich, I.G.; Rogovin, K.A.; Shabalina, I.G.; et al. Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents. Aging 2011, 3, 1110–1119.
  111. Anisimov, V.N.; Bakeeva, L.E.; Egormin, P.A.; Filenko, O.F.; Isakova, E.F.; Manskikh, V.N.; Mikhelson, V.M.; Panteleeva, A.A.; Pasyukova, E.G.; Pilipenko, D.I.; et al. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence. Biochemistry (Mosc.) 2008, 73, 1329–1342.
  112. Neroev, V.V.; Archipova, M.M.; Bakeeva, L.E.; Fursova, A.; Grigorian, E.N.; Grishanova, A.Y.; Iomdina, E.N.; Ivashchenko, Z.N.; Katargina, L.A.; Khoroshilova-Maslova, I.P.; et al. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals. Biochemistry (Mosc.) 2008, 73, 1317–1328.
  113. Study of SkQ1 as Treatment for Dry-Eye Syndrome. Available online: (accessed on 20 January 2021).
  114. Vehicle-Controlled Study of SkQ1 as Treatment for Dry-Eye Syndrome. Available online: (accessed on 20 January 2021).
  115. A Clinical Study to Assess the Safety and Efficacy of an Ophthalmic Solution (SkQ1) in the Treatment of Dry Eye Syndrome (DES). Available online: (accessed on 20 January 2021).
  116. Rouen, P.A.; White, M.L. Dry Eye Disease: Prevalence, Assessment, and Management. Home Healthc. Now 2018, 36, 74–83.
  117. Petrov, A.; Perekhvatova, N.; Skulachev, M.; Stein, L.; Ousler, G. SkQ1 Ophthalmic Solution for Dry Eye Treatment: Results of a Phase 2 Safety and Efficacy Clinical Study in the Environment and During Challenge in the Controlled Adverse Environment Model. Adv. Ther. 2016, 33, 96–115.
  118. Wang, J.; Li, S.; Yang, T.; Yang, J. Synthesis and antioxidant activities of Coenzyme Q analogues. Eur. J. Med. Chem. 2014, 86, 710–713.
  119. Kawamukai, M. Biosynthesis of coenzyme Q in eukaryotes. Biosci. Biotechnol. Biochem. 2016, 80, 23–33.
  120. Aberg, F.; Appelkvist, E.L.; Dallner, G.; Ernster, L. Distribution and redox state of ubiquinones in rat and human tissues. Arch. Biochem. Biophys. 1992, 295, 230–234.
  121. Chan, T.S.; Teng, S.; Wilson, J.X.; Galati, G.; Khan, S.; O’Brien, P.J. Coenzyme Q cytoprotective mechanisms for mitochondrial complex I cytopathies involves NAD(P)H: Quinone oxidoreductase 1(NQO1). Free Radic. Res. 2002, 36, 421–427.
  122. Takahashi, T.; Mine, Y.; Okamoto, T. Intracellular reduction of coenzyme Q homologues with a short isoprenoid side chain induces apoptosis of HeLa cells. J. Biochem. 2018, 163, 329–339.
  123. Kagan, V.E.; Serbinova, E.A.; Koynova, G.M.; Kitanova, S.A.; Tyurin, V.A.; Stoytchev, T.S.; Quinn, P.J.; Packer, L. Antioxidant action of ubiquinol homologues with different isoprenoid chain length in biomembranes. Free Radic. Biol. Med. 1990, 9, 117–126.
  124. Kishi, T.; Okamoto, T.; Takahashi, T.; Goshima, K.; Yamagami, T. Cardiostimulatory action of coenzyme Q homologues on cultured myocardial cells and their biochemical mechanisms. Clin. Investig. 1993, 71, S71–S75.
  125. Esaka, Y.; Nagahara, Y.; Hasome, Y.; Nishio, R.; Ikekita, M. Coenzyme Q2 induced p53-dependent apoptosis. Biochim. Biophys. Acta 2005, 1724, 49–58.
  126. Lenaz, G. Quinone specificity of complex I. Biochim. Biophys. Acta 1998, 1364, 207–221.
  127. Cadenas, E.; Boveris, A.; Ragan, C.I.; Stoppani, A.O. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch. Biochem. Biophys. 1977, 180, 248–257.
  128. Lenaz, G.; Bovina, C.; D’Aurelio, M.; Fato, R.; Formiggini, G.; Genova, M.L.; Giuliano, G.; Pich, M.M.; Paolucci, U.; Castelli, G.P.; et al. Role of mitochondria in oxidative stress and aging. Ann. N. Y. Acad. Sci. 2002, 959, 199–213.
  129. O’Brien, P.J. Molecular mechanisms of quinone cytotoxicity. Chem. Biol. Interact. 1991, 80, 1–41.
  130. Monks, T.J.; Hanzlik, R.P.; Cohen, G.M.; Ross, D.; Graham, D.G. Quinone chemistry and toxicity. Toxicol. Appl. Pharmacol. 1992, 112, 2–16.
  131. Long, D.J., II; Jaiswal, A.K. NRH:quinone oxidoreductase2 (NQO2). Chem. Biol. Interact. 2000, 129, 99–112.
  132. Colucci, M.A.; Moody, C.J.; Couch, G.D. Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: From synthetic organic chemistry to compounds with anticancer potential. Org. Biomol. Chem. 2008, 6, 637–656.
  133. Boutin, J.A.; Chatelain-Egger, F.; Vella, F.; Delagrange, P.; Ferry, G. Quinone reductase 2 substrate specificity and inhibition pharmacology. Chem. Biol. Interact. 2005, 151, 213–228.
  134. Cerqua, C.; Casarin, A.; Pierrel, F.; Fonseca, L.V.; Viola, G.; Salviati, L.; Trevisson, E. Vitamin K2 cannot substitute Coenzyme Q10 as electron carrier in the mitochondrial respiratory chain of mammalian cells. Sci. Rep. 2019, 9, 6553.
  135. Grant, J.; Saldanha, J.W.; Gould, A.P. A Drosophila model for primary coenzyme Q deficiency and dietary rescue in the developing nervous system. Dis. Model. Mech. 2010, 3, 799–806.
  136. Shrader, W.D.; Amagata, A.; Barnes, A.; Enns, G.M.; Hinman, A.; Jankowski, O.; Kheifets, V.; Komatsuzaki, R.; Lee, E.; Mollard, P.; et al. alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorg. Med. Chem. Lett. 2011, 21, 3693–3698.
  137. Enns, G.M.; Kinsman, S.L.; Perlman, S.L.; Spicer, K.M.; Abdenur, J.E.; Cohen, B.H.; Amagata, A.; Barnes, A.; Kheifets, V.; Shrader, W.D.; et al. Initial experience in the treatment of inherited mitochondrial disease with EPI-743. Mol. Genet. Metab. 2012, 105, 91–102.
  138. Lu, S.C. Glutathione synthesis. Biochim. Biophys. Acta 2013, 1830, 3143–3153.
  139. Oestreicher, J.; Morgan, B. Glutathione: Subcellular distribution and membrane transport (1). Biochem. Cell Biol. 2019, 97, 270–289.
  140. Kahn-Kirby, A.H.; Amagata, A.; Maeder, C.I.; Mei, J.J.; Sideris, S.; Kosaka, Y.; Hinman, A.; Malone, S.A.; Bruegger, J.J.; Wang, L.; et al. Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. PLoS ONE 2019, 14, e0214250.
  141. Hirschhorn, T.; Stockwell, B.R. The development of the concept of ferroptosis. Free Radic. Biol. Med. 2019, 133, 130–143.
  142. Chen, S.; Chen, Y.; Zhang, Y.; Kuang, X.; Liu, Y.; Guo, M.; Ma, L.; Zhang, D.; Li, Q. Iron Metabolism and Ferroptosis in Epilepsy. Front. Neurosci. 2020, 14, 601193.
  143. Wang, H.; Liu, C.; Zhao, Y.; Gao, G. Mitochondria regulation in ferroptosis. Eur. J. Cell Biol. 2020, 99, 151058.
  144. Abdalkader, M.; Lampinen, R.; Kanninen, K.M.; Malm, T.M.; Liddell, J.R. Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration. Front. Neurosci. 2018, 12, 466.
  145. Bebber, C.M.; Muller, F.; Clemente, L.P.; Weber, J.; von Karstedt, S. Ferroptosis in Cancer Cell Biology. Cancers (Basel) 2020, 12, 164.
  146. Masaldan, S.; Bush, A.I.; Devos, D.; Rolland, A.S.; Moreau, C. Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration. Free Radic. Biol. Med. 2019, 133, 221–233.
  147. Enns, G.M.; Cowan, T.M. Glutathione as a Redox Biomarker in Mitochondrial Disease-Implications for Therapy. J. Clin. Med. 2017, 6, 50.
  148. Sadun, A.A.; Chicani, C.F.; Ross-Cisneros, F.N.; Barboni, P.; Thoolen, M.; Shrader, W.D.; Kubis, K.; Carelli, V.; Miller, G. Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy. Arch. Neurol. 2012, 69, 331–338.
  149. Martinelli, D.; Catteruccia, M.; Piemonte, F.; Pastore, A.; Tozzi, G.; Dionisi-Vici, C.; Pontrelli, G.; Corsetti, T.; Livadiotti, S.; Kheifets, V.; et al. EPI-743 reverses the progression of the pediatric mitochondrial disease—Genetically defined Leigh Syndrome. Mol. Genet. Metab. 2012, 107, 383–388.
  150. Pastore, A.; Petrillo, S.; Tozzi, G.; Carrozzo, R.; Martinelli, D.; Dionisi-Vici, C.; Di Giovamberardino, G.; Ceravolo, F.; Klein, M.B.; Miller, G.; et al. Glutathione: A redox signature in monitoring EPI-743 therapy in children with mitochondrial encephalomyopathies. Mol. Genet. Metab. 2013, 109, 208–214.
  151. An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children with Autism Spectrum Disorder. Available online: (accessed on 20 January 2021).
  152. Safety and Efficacy of EPI-743 in Patients with Friedreich’s Ataxia. Available online: (accessed on 20 January 2021).
  153. Kouga, T.; Takagi, M.; Miyauchi, A.; Shimbo, H.; Iai, M.; Yamashita, S.; Murayama, K.; Klein, M.B.; Miller, G.; Goto, T.; et al. Japanese Leigh syndrome case treated with EPI-743. Brain Dev. 2018, 40, 145–149.
  154. A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants with Refractory Epilepsy. Available online: (accessed on 20 January 2021).
  155. Phase 2 Study of EPI-743 in Children with Pearson Syndrome. Available online: (accessed on 20 January 2021).
  156. EPI-743 in Friedreich’s Ataxia Point Mutations. Available online: (accessed on 20 January 2021).
  157. EPI-743 for Mitochondrial Respiratory Chain Diseases. Available online: (accessed on 20 January 2021).
  158. EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment. Available online: (accessed on 20 January 2021).
  159. Finsterer, J.; Zarrouk-Mahjoub, S. Is vatiquinone truly beneficial for Leigh syndrome? Brain Dev. 2018, 40, 443.
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