The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.

TitleThe mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsSolesio, ME, Prime, TA, Logan, A, Murphy, MP, Arroyo-Jimenez, MDel Mar, Jordán, J, Galindo, MF
JournalBiochim Biophys Acta
Volume1832
Issue1
Pagination174-82
Date Published2013 Jan
ISSN0006-3002
KeywordsAntioxidants, Cell Line, Humans, Mitochondria, Mitochondrial Dynamics, Organophosphorus Compounds, Oxidative Stress, Oxidopamine, Parkinson Disease, Reactive Oxygen Species, Ubiquinone
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.

DOI10.1016/j.bbadis.2012.07.009
Alternate JournalBiochim. Biophys. Acta
Citation Key10.1016/j.bbadis.2012.07.009
PubMed ID22846607
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom