Cited by 618Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyNeuroprotection in Cerebral Ischemia

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

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. Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., Sammut, I. A. Targeting an antioxidant to mitochondria decreases cardiac ischemia‐reperfusion injury. FASEB J. 19, 1088–1095 (2005)

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Crossref · 10.1096/fj.05-3718com

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39 of 39 references verified0 citation errors · 0 not checkable

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Metadata

Authors
Adlam, V. J., Harrison, J. C., Porteous, C. M., James, A. M., Smith, R. A. J., Murphy, M. P., & Sammut, I. A.
Affiliations
  • University of Otago (NZ)
  • MRC Mitochondrial Biology Unit (GB)
Venue
The FASEB Journal
Publisher
Wiley
Published
2005-07
Volume
19
Issue
9
Pages
1088-1095
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2060179384
Cited by
618
References
39
Citations by year
2026: 10 · 2025: 26 · 2024: 11 · 2023: 17 · 2022: 28 · 2021: 28 · 2020: 38 · 2019: 36 · 2018: 32 · 2017: 25 · 2016: 32 · 2015: 40 · 2014: 45 · 2013: 33 · 2012: 34
FWCI
19.15
Type
journal article
Language
en
Open access
closed
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords
mitochondria-targeted antioxidants, MitoQ, myocardial ischemia-reperfusion injury, mitochondrial oxidative damage, triphenylphosphonium cation, ubiquinol, mitochondrial membrane potential, cardiac dysfunction, mitochondrial cell death, Parkinson's disease, Friedreich's ataxia, diabetes mellitus
MeSH terms
Animals, Antioxidants, Heart, Male, Mitochondria, Organophosphorus Compounds, Oxygen Consumption, Ubiquinone, Myocardial Reperfusion Injury, Rats, Wistar, Protective Agents, Cytochromes c, Rats

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