Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants.

TitleMitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants.
Publication TypeJournal Article
Year of Publication2003
AuthorsJauslin, ML, Meier, T, Smith, RAJ, Murphy, MP
JournalFASEB J
Volume17
Issue13
Pagination1972-4
Date Published2003 Oct
ISSN1530-6860
KeywordsAntioxidants, Benzoquinones, Cell Death, Drug Delivery Systems, Fibroblasts, Friedreich Ataxia, Humans, Mitochondria, Models, Biological, Organophosphorus Compounds, Oxidative Stress, Ubiquinone, Vitamin E
Abstract

Friedreich Ataxia (FRDA), the most common inherited ataxia, arises from defective expression of the mitochondrial protein frataxin, which leads to increased mitochondrial oxidative damage. Therefore, antioxidants targeted to mitochondria should be particularly effective at slowing disease progression. To test this hypothesis, we compared the efficacy of mitochondria-targeted and untargeted antioxidants derived from coenzyme Q10 and from vitamin E at preventing cell death due to endogenous oxidative stress in cultured fibroblasts from FRDA patients in which glutathione synthesis was blocked. The mitochondria-targeted antioxidant MitoQ was several hundredfold more potent than the untargeted analog idebenone. The mitochondria-targeted antioxidant MitoVit E was 350-fold more potent than the water soluble analog Trolox. This is the first demonstration that mitochondria-targeted antioxidants prevent cell death that arises in response to endogenous oxidative damage. Targeted antioxidants may have therapeutic potential in FRDA and in other disorders involving mitochondrial oxidative damage.

DOI10.1096/fj.03-0240fje
Alternate JournalFASEB J.
Citation Key10.1096/fj.03-0240fje
PubMed ID12923074