Targeting antioxidants to mitochondria by conjugation to lipophilic cations.

TitleTargeting antioxidants to mitochondria by conjugation to lipophilic cations.
Publication TypeJournal Article
Year of Publication2007
AuthorsMurphy, MP, Smith, RAJ
JournalAnnu Rev Pharmacol Toxicol
Volume47
Pagination629-56
Date Published2007
ISSN0362-1642
KeywordsAntioxidants, Cations, Drug Carriers, Drug Delivery Systems, Humans, Membrane Potentials, Mitochondria, Mitochondrial Diseases, Reactive Oxygen Species, Tissue Distribution
Abstract

Mitochondrial oxidative damage contributes to a range of degenerative diseases. Consequently, the selective inhibition of mitochondrial oxidative damage is a promising therapeutic strategy. One way to do this is to invent antioxidants that are selectively accumulated into mitochondria within patients. Such mitochondria-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to an antioxidant moiety, such as ubiquinol or alpha-tocopherol. These compounds pass easily through all biological membranes, including the blood-brain barrier, and into muscle cells and thus reach those tissues most affected by mitochondrial oxidative damage. Furthermore, because of their positive charge they are accumulated several-hundredfold within mitochondria driven by the membrane potential, enhancing the protection of mitochondria from oxidative damage. These compounds protect mitochondria from damage following oral delivery and may therefore form the basis for mitochondria-protective therapies. Here we review the background and work to date on this class of mitochondria-targeted antioxidants.

DOI10.1146/annurev.pharmtox.47.120505.105110
Alternate JournalAnnu. Rev. Pharmacol. Toxicol.
Citation Key10.1146/annurev.pharmtox.47.120505.105110
PubMed ID17014364
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom