1.
Sources and Structure
1.1
Sources
MitoQ is a term used to refer to mitoquinone mesylate ( with {10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienlyl) decyl triphenylphosphonium methanesulfonate}) as the prolonged chemical name), which is a derivative of CoQ10 where said molecule is covalently bonded to a triphenylphosphonium cation.
The CoQ10 moiety is delivered to the matrix side of the inner mitochondrial matrix,[1] which is the site of most mitochondrial oxidative stress.[2] Despite accumulation in the mitrochondria, however, MitoQ is a poor substrate for the electron transport chain (at complex I) and is not thought to contribute much to bioenergetics.[3][4]
1.2
Biological Significance
Oral administration of MitoQ in otherwise healthy wild type mice over 28 weeks fails to significantly alter mitochondrial function or gene expression, and no overall influence on systemic energy metabolism.[5]
2.
Neurology
2.1
Dementia
Alzheimer's is known to be associated with mitochondrial abnormalities in neurons associated with oxidative stress[6][7]
Beta-amyloid toxicity has been noted to be reduced in N2a cells with MitoQ incubation[8] and at 1-100nM mostly abolished cell death from amyloid proteins (no dose dependence noted).[9]
100μM of MitoQ daily to a mouse model of Alzheimer's has been noted to improve spatial memory and cognitive performance associated with a reduction in lipid peroxidation.[9]
References
- ^Murphy MP, Smith RATargeting antioxidants to mitochondria by conjugation to lipophilic cationsAnnu Rev Pharmacol Toxicol.(2007)
- ^Free Radicals in Biology and Medicine
- ^Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species
- ^James AM, Cochemé HM, Smith RA, Murphy MPInteractions 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 toolsJ Biol Chem.(2005 Jun 3)
- ^Rodriguez-Cuenca S, Cochemé HM, Logan A, Abakumova I, Prime TA, Rose C, Vidal-Puig A, Smith AC, Rubinsztein DC, Fearnley IM, Jones BA, Pope S, Heales SJ, Lam BY, Neogi SG, McFarlane I, James AM, Smith RA, Murphy MPConsequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type miceFree Radic Biol Med.(2010 Jan 1)
- ^Hoyer SOxidative metabolism deficiencies in brains of patients with Alzheimer's diseaseActa Neurol Scand Suppl.(1996)
- ^Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MAMitochondrial abnormalities in Alzheimer's diseaseJ Neurosci.(2001 May 1)
- ^Manczak M, Mao P, Calkins MJ, Cornea A, Reddy AP, Murphy MP, Szeto HH, Park B, Reddy PHMitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neuronsJ Alzheimers Dis.(2010)
- ^McManus MJ, Murphy MP, Franklin JLThe mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's diseaseJ Neurosci.(2011 Nov 2)