Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury.

TitleTargeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury.
Publication TypeJournal Article
Year of Publication2005
AuthorsAdlam, VJ, Harrison, JC, Porteous, CM, James, AM, Smith, RAJ, Murphy, MP, Sammut, IA
JournalFASEB J
Volume19
Issue9
Pagination1088-95
Date Published2005 Jul
ISSN1530-6860
KeywordsAnimals, Antioxidants, Cytochromes c, Heart, Male, Mitochondria, Myocardial Reperfusion Injury, Organophosphorus Compounds, Oxygen Consumption, Protective Agents, Rats, Rats, Wistar, Ubiquinone
Abstract

Mitochondrial oxidative damage contributes to a wide range of pathologies, including cardiovascular disorders and neurodegenerative diseases. Therefore, protecting mitochondria from oxidative damage should be an effective therapeutic strategy. However, conventional antioxidants have limited efficacy due to the difficulty of delivering them to mitochondria in situ. To overcome this problem, we developed mitochondria-targeted antioxidants, typified by MitoQ, which comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the TPP cation concentrates MitoQ several hundred-fold within mitochondria, selectively preventing mitochondrial oxidative damage. To test whether MitoQ was active in vivo, we chose a clinically relevant form of mitochondrial oxidative damage: cardiac ischemia-reperfusion injury. Feeding MitoQ to rats significantly decreased heart dysfunction, cell death, and mitochondrial damage after ischemia-reperfusion. This protection was due to the antioxidant activity of MitoQ within mitochondria, as an untargeted antioxidant was ineffective and accumulation of the TPP cation alone gave no protection. Therefore, targeting antioxidants to mitochondria in vivo is a promising new therapeutic strategy in the wide range of human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia where mitochondrial oxidative damage underlies the pathology.

DOI10.1096/fj.05-3718com
Alternate JournalFASEB J.
Citation Key10.1096/fj.05-3718com
PubMed ID15985532