Prevention of mitochondrial oxidative damage using targeted antioxidants.

TitlePrevention of mitochondrial oxidative damage using targeted antioxidants.
Publication TypeJournal Article
Year of Publication2002
AuthorsKelso, GF, Porteous, CM, Hughes, G, Ledgerwood, EC, Gane, AM, Smith, RAJ, Murphy, MP
JournalAnn N Y Acad Sci
Volume959
Pagination263-74
Date Published2002 Apr
ISSN0077-8923
KeywordsAnimals, Antioxidants, Apoptosis, Electron Transport, Female, Humans, Indicators and Reagents, Jurkat Cells, Mice, Mitochondria, Liver, Molecular Structure, Onium Compounds, Organophosphorus Compounds, Oxidation-Reduction, Rats, Thiobarbituric Acid Reactive Substances, Trityl Compounds, Ubiquinone
Abstract

Mitochondrial-targeted antioxidants that selectively block mitochondrial oxidative damage and prevent some types of cell death have been developed. These antioxidants are ubiquinone and tocopherol derivatives and are targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation. Because of the large mitochondrial membrane potential, these cations accumulated within mitochondria inside cells, where the antioxidant moiety prevents lipid peroxidation and protects mitochondria from oxidative damage. The mitochondrially localized ubiquinone also protected mammalian cells from hydrogen peroxide-induced apoptosis while an untargeted ubiquinone analogue was ineffective against apoptosis. When fed to mice these compounds accumulated within the brain, heart, and liver; therefore, using these mitochondrial-targeted antioxidants may help investigations of the role of mitochondrial oxidative damage in animal models of aging.

DOI10.1111/j.1749-6632.2002.tb02098.x
Alternate JournalAnn. N. Y. Acad. Sci.
Citation Key10.1111/j.1749-6632.2002.tb02098.x
PubMed ID11976201