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MitoQ
MitoQ is a mitochondria-targeted antioxidant designed to accumulate within mitochondria ''in vivo'' in order to protect against oxidative damage. It is the first molecule specifically designed to decrease mitochondrial oxidative damage to have undergone clinical trials in humans.〔E.J. Gane, F. Weilert, D.W. Orr, G.F. Keogh, M. Gibson, M.M. Lockhart, C.M. Frampton, K.M. Taylor, R.A. Smith, M.P. Murphy, The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients, Liver Int, 30 (2010) 1019–1026.〕〔B.J. Snow, F.L. Rolfe, M.M. Lockhart, C.M. Frampton, J.D. O'Sullivan, V. Fung, R.A. Smith, M.P. Murphy, K.M. Taylor, A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease, Movement disorders : official journal of the Movement Disorder Society, 25 (2010) 1670–1674.〕〔R.A. Smith, M.P. Murphy, Animal and human studies with the mitochondria-targeted antioxidant MitoQ, Annals of the New York Academy of Sciences, 1201 (2010) 96-103.〕 Mitochondria are an essential organelle within most cells that use oxygen to break down carbohydrates and fat to release energy in a form the cell can use. In doing this mitochondria release disruptive free radicals that contribute to oxidative damage in a wide range of diseases and pathologies. MitoQ is being evaluated as a therapy for some of these disorders. The molecule comprises a positively charged lipophilic cation that drives its extensive accumulation within the negatively charged mitochondria inside cells. The active antioxidant component of MitoQ is ubiquinone, which is identical to the active antioxidant in Coenzyme Q10. The lipophilic cation enables MitoQ to be accumulated selectively and extensively by mitochondria, in contrast to other antioxidants which distribute evenly throughout the cell. It is this approximately thousand-fold greater concentration of MitoQ within mitochondria that makes it more effective at preventing mitochondrial oxidative damage when compared to untargeted antioxidants such as Coenzyme Q10. == Mitochondrial oxidative damage ==
Mitochondria are essential organelles within most of our cells that use the oxygen we breathe to break down the fat and carbohydrate in our diet. This process, called oxidative phosphorylation, releases the energy stored in food in a form that can be used within our cells, namely adenosine triphosphate (ATP). In addition, mitochondria are also central to many other aspects of metabolism and cell death in pathology and disease as they regulate programmed cell death or apoptosis. Due to all these essential functions, damage or disruption to mitochondria is a significant contributor to the cell death and tissue damage that underlies many diseases and pathologies. Oxidative stress occurs when reactive oxygen species such as free radicals react with and damage biological molecules, cells and tissues.〔B.H. Halliwell, J.M.C. Gutteridge, Free radicals in Biology and Medicine, 4th ed., Oxford University Press, Oxford, 2007.〕 As mitochondria are the major source of the free radical superoxide within cells, mitochondrial oxidative stress is thought to be a major contributing factor underlying a wide range of diseases and pathologies.〔M.P. Murphy, How mitochondria produce reactive oxygen species, Biochem J, 417 (2009) 1-13.〕〔D.C. Wallace, W. Fan, V. Procaccio, Mitochondrial energetics and therapeutics, Annu Rev Pathol, 5 (2010) 297-348.〕〔T. Finkel, Opinion: Radical medicine: treating ageing to cure disease, Nat Rev Mol Cell Biol, 6 (2005) 971-976.〕 These include acute disorders such as heart attack, stroke and sepsis, and also chronic disorders such as diabetes, metabolic syndrome, inflammation, and many of the degenerative processes and diseases associated with ageing such as Parkinson's disease and Alzheimer's disease. Consequently, antioxidants, which are designed to block the damage caused by reactive oxygen species, should be effective therapies for a wide range of diseases by decreasing mitochondrial oxidative damage.〔M.P. Murphy, Mitochondria--a neglected drug target, Curr Opin Investig Drugs, 10 (2009) 1022–1024.〕 However, when antioxidants have been tried as therapies in patients who are not deficient in endogenous antioxidants they have generally been disappointing.〔G. Bjelakovic, D. Nikolova, L.L. Gluud, R.G. Simonetti, C. Gluud, Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases, Cochrane Database of Systematic Reviews, (2008).〕〔H.M. Cocheme, M.P. Murphy, Can antioxidants be effective therapeutics?, Curr Opin Investig Drugs, 11 (2010) 426-431.〕 The relatively poor efficacy of conventional antioxidants may be because not enough antioxidant gets to the mitochondria, the main site of oxidative damage in the cell. To overcome this difficulty mitochondria-targeted antioxidants such as MitoQ were developed.〔R.A. Smith, R.C. Hartley, H.M. Cocheme, M.P. Murphy, Mitochondrial pharmacology, Trends in pharmacological sciences, 33 (2012) 341-352.〕〔M.P. Murphy, R.A. Smith, Targeting antioxidants to mitochondria by conjugation to lipophilic cations, Annual review of pharmacology and toxicology, 47 (2007) 629-656.〕
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