Cited by 1,173Mitochondrial Function and PathologyCoenzyme Q10 studies and effectsNeuroprotection in Cerebral Ischemia

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Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations

Murphy, Michael P., Smith, Robin A.J.·2007·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev.pharmtox.47.120505.105110

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Abstract

Mitochondrial oxidative damage contributes to a range of degenerative diseases. Consequently, the selective inhibition of mitochondrial oxidative damage is a promising therapeutic strategy. One way to do this is to invent antioxidants that are selectively accumulated into mitochondria within patients. Such mitochondria-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to an antioxidant moiety, such as ubiquinol or α-tocopherol. These compounds pass easily through all biological membranes, including the blood-brain barrier, and into muscle cells and thus reach those tissues most affected by mitochondrial oxidative damage. Furthermore, because of their positive charge they are accumulated several-hundredfold within mitochondria driven by the membrane potential, enhancing the protection of mitochondria from oxidative damage. These compounds protect mitochondria from damage following oral delivery and may therefore form the basis for mitochondria-protective therapies. Here we review the background and work to date on this class of mitochondria-targeted antioxidants.

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Authors: Murphy, M. P., & Smith, R. A. J.
Affiliations: MRC Mitochondrial Biology Unit (GB)
University of Otago (NZ)
ORCID: Murphy, Michael P.
Venue: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
Published: 2007-02-01
Volume: 47
Issue: 1
Pages: 629-656
ISSN: 0362-1642 (ISSN-L)
1545-4304
DOI: 10.1146/annurev.pharmtox.47.120505.105110
OpenAlex: W2140014506
Cited by: 1,173
References: 130
Citations by year: 2026: 64 · 2025: 62 · 2024: 72 · 2023: 42 · 2022: 65 · 2021: 67 · 2020: 61 · 2019: 57 · 2018: 61 · 2017: 62 · 2016: 67 · 2015: 67 · 2014: 62 · 2013: 59 · 2012: 68
FWCI: 2.97
Type: journal article
Language: en
Open access: closed
Locations: The Annual Review of Pharmacology and Toxicology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords: mitochondria-targeted antioxidants, triphenylphosphonium cation, lipophilic cations, mitochondrial oxidative damage, ubiquinol, alpha-tocopherol, mitochondrial membrane potential, blood-brain barrier, oral drug delivery, degenerative diseases, mitochondrial protection
MeSH terms: Antioxidants, Cations, Drug Carriers, Humans, Membrane Potentials, Mitochondria, Tissue Distribution, Drug Delivery Systems, Reactive Oxygen Species, Mitochondrial Diseases

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Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations

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