Cited by 1,091Coenzyme Q10 studies and effectsMitochondrial Function and PathologyCell death mechanisms and regulation

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Selective Targeting of a Redox-active Ubiquinone to Mitochondria within Cells

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Abstract

With the recognition of the central role of mitochondria in apoptosis, there is a need to develop specific tools to manipulate mitochondrial function within cells. Here we report on the development of a novel antioxidant that selectively blocks mitochondrial oxidative damage, enabling the roles of mitochondrial oxidative stress in different types of cell death to be inferred. This antioxidant, named mitoQ, is a ubiquinone derivative targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation through an aliphatic carbon chain. Due to the large mitochondrial membrane potential, the cation was accumulated within mitochondria inside cells, where the ubiquinone moiety inserted into the lipid bilayer and was reduced by the respiratory chain. The ubiquinol derivative thus formed was an effective antioxidant that prevented lipid peroxidation and protected mitochondria from oxidative damage. After detoxifying a reactive oxygen species, the ubiquinol moiety was regenerated by the respiratory chain enabling its antioxidant activity to be recycled. In cell culture studies, the mitochondrially localized antioxidant protected mammalian cells from hydrogen peroxide-induced apoptosis but not from apoptosis induced by staurosporine or tumor necrosis factor-alpha. This was compared with untargeted ubiquinone analogs, which were ineffective in preventing apoptosis. These results suggest that mitochondrial oxidative stress may be a critical step in apoptosis induced by hydrogen peroxide but not for apoptosis induced by staurosporine or tumor necrosis factor-alpha. We have shown that selectively manipulating mitochondrial antioxidant status with targeted and recyclable antioxidants is a feasible approach to investigate the role of mitochondrial oxidative damage in apoptotic cell death. This approach will have further applications in investigating mitochondrial dysfunction in a range of experimental models.

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Crossref · 10.1074/jbc.m009093200

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Research works printed but not linked: 2

  1. Ernster, 1992, Biofactors, 3, 241
  2. Schopfer, 2000, Biochem. J., 349, 35, 10.1042/bj3490035 · DOI

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Metadata

Authors
Kelso, G. F., Porteous, C. M., Coulter, C. V., Hughes, G., Porteous, W. K., Ledgerwood, E. C., Smith, R. A. J., & Murphy, M. P.
Affiliations
University of Otago (NZ)
Corresponding author
Murphy, Michael P.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-02
Volume
276
Issue
7
Pages
4588-4596
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2017692041
Cited by
1,091
References
51
Citations by year
2026: 33 · 2025: 33 · 2024: 53 · 2023: 52 · 2022: 57 · 2021: 65 · 2020: 60 · 2019: 43 · 2018: 57 · 2017: 50 · 2016: 52 · 2015: 51 · 2014: 43 · 2013: 37 · 2012: 47
FWCI
7.80
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
MitoQ, mitochondrial targeting, triphenylphosphonium cation, mitochondrial membrane potential, mitochondrial oxidative stress, hydrogen peroxide-induced apoptosis, staurosporine-induced apoptosis, lipid peroxidation, electron transport chain, mitochondrial dysfunction
MeSH terms
Animals, Antioxidants, Biological Transport, Active, Cattle, Cell Survival, Electron Transport, Humans, Hydrogen Peroxide, Mitochondria, Multienzyme Complexes, Organophosphorus Compounds, Oxidation-Reduction, Tumor Cells, Cultured, Ubiquinone, Apoptosis, Oxidative Stress, Jurkat Cells, Rats

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