title: The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder for which available treatments provide symptom relief but do not stop disease progression. Mitochondria, and in particular mitochondrial dynamics, have been postulated as plausible pharmacological targets. Mitochondria-targeted antioxidants have been developed to prevent mitochondrial oxidative damage, and to alter the involvement of reactive oxygen species (ROS) in signaling pathways. In this study, we have dissected the effect of MitoQ, which is produced by covalent attachment of ubiquinone to a triphenylphosphonium lipophilic cation by a ten carbon alkyl chain. MitoQ was tested in an in vitro PD model which involves addition of 6-hydroxydopamine (6-OHDA) to SH-SY5Y cell cultures. At sublethal concentrations of 50μM, 6-OHDA did not induce increases in protein carbonyl, mitochondrial lipid peroxidation or mitochondrial DNA damage. However, after 3h of treatment, 6-OHDA disrupts the mitochondrial morphology and activates the machinery of mitochondrial fission, but not fusion. Addition of 6-OHDA did not increase the levels of fission 1, mitofusins 1 and 2 or optic atrophy 1 proteins, but does lead to the translocation of dynamin related protein 1 from the cytosol to the mitochondria. Pre-treatment with MitoQ (50nM, 30min) results in the inhibition of the mitochondrial translocation of Drp1. Furthermore, MitoQ also inhibited the translocation of the pro-apoptotic protein Bax to the mitochondria. These findings provide mechanistic evidence for a role for redox events contributing to mitochondrial fission and suggest the potential of mitochondria-targeted therapeutics in diseases that involve mitochondrial fragmentation due to oxidative stress.
authors: Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
authors: María E
authors: ME
authors: Solesio
authors: Tracy A
authors: TA
authors: Prime
authors: Angela
authors: A
authors: Logan
authors: Michael P
authors: MP
authors: Murphy
authors: María
authors: M
authors: Del Mar Arroyo-Jimenez
authors: Joaquín
authors: J
authors: Jordán
authors: María F
authors: MF
authors: Galindo
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C429014:mitoquinone; D016627:Oxidopamine