Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury
- PMID: 15985532
- DOI: 10.1096/fj.05-3718com
Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury
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.
Similar articles
-
Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties.J Biol Chem. 2001 Feb 16;276(7):4588-96. doi: 10.1074/jbc.M009093200. Epub 2000 Nov 22. J Biol Chem. 2001. PMID: 11092892
-
Fine-tuning the hydrophobicity of a mitochondria-targeted antioxidant.FEBS Lett. 2004 Jul 30;571(1-3):9-16. doi: 10.1016/j.febslet.2004.06.045. FEBS Lett. 2004. PMID: 15280009
-
Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.Redox Biol. 2015 Aug;5:163-168. doi: 10.1016/j.redox.2015.04.008. Epub 2015 Apr 29. Redox Biol. 2015. PMID: 25965144 Free PMC article.
-
Animal and human studies with the mitochondria-targeted antioxidant MitoQ.Ann N Y Acad Sci. 2010 Jul;1201:96-103. doi: 10.1111/j.1749-6632.2010.05627.x. Ann N Y Acad Sci. 2010. PMID: 20649545 Review.
-
MitoQ--a mitochondria-targeted antioxidant.IDrugs. 2007 Jun;10(6):399-412. IDrugs. 2007. PMID: 17642004 Review.
Cited by
-
Myeloperoxidase as a Promising Therapeutic Target after Myocardial Infarction.Antioxidants (Basel). 2024 Jun 28;13(7):788. doi: 10.3390/antiox13070788. Antioxidants (Basel). 2024. PMID: 39061857 Free PMC article. Review.
-
Inhibition of the mPTP and Lipid Peroxidation Is Additively Protective Against I/R Injury.Circ Res. 2024 May 10;134(10):1292-1305. doi: 10.1161/CIRCRESAHA.123.323882. Epub 2024 Apr 15. Circ Res. 2024. PMID: 38618716 Free PMC article.
-
Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease.Cells. 2024 Feb 17;13(4):353. doi: 10.3390/cells13040353. Cells. 2024. PMID: 38391966 Free PMC article. Review.
-
IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish.Int J Mol Sci. 2023 Dec 7;24(24):17215. doi: 10.3390/ijms242417215. Int J Mol Sci. 2023. PMID: 38139043 Free PMC article.
-
Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules. 2023 Sep 19;13(9):1409. doi: 10.3390/biom13091409. Biomolecules. 2023. PMID: 37759809 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical