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Mitochondria‐targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants
Author(s) -
Jauslin Matthias L.,
Meier Thomas,
Smith Robin A. J.,
Murphy P. Michael
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0240fje
Subject(s) - coenzyme q10 , oxidative stress , mitochondrion , frataxin , idebenone , trolox , oxidative phosphorylation , programmed cell death , mitochondrial ros , endogeny , biochemistry , mitochondrial disease , reactive oxygen species , antioxidant , chemistry , pharmacology , biology , apoptosis , mitochondrial dna , aconitase , gene , antioxidant capacity
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 Q 10 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.