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Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies
Abstract
Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis.
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“In particular, SkQ1 and SkQR1 have been reported to reduce H2O2-induced senescence and apoptosis in vitro and to prevent senescence and tissue damage during aging [75].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [75]
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Metadata
- Authors
- V. Skulachev, M., N. Antonenko, Y., N. Anisimov, V., V. Chernyak, B., A. Cherepanov, D., A. Chistyakov, V., V. Egorov, M., G. Kolosova, N., A. Korshunova, G., G. Lyamzaev, K., Y. Plotnikov, E., A. Roginsky, V., Y. Savchenko, A., I. Severina, I., F. Severin, F., P. Shkurat, T., N. Tashlitsky, V., M. Shidlovsky, K., Y. Vyssokikh, M., A. Zamyatnin, A., B. Zorov, D., & P. Skulachev, V.
- Venue
- Current Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-06-01
- Volume
- 12
- Issue
- 6
- Pages
- 800-826
- ISSN
- 1389-4501 (ISSN-L)
- OpenAlex
- W2152273206
- Cited by
- 156
- References
- 100
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 4 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 13 · 2014: 17 · 2013: 18 · 2012: 21
- FWCI
- 8.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- plastoquinone, SkQ1, mitochondria-targeted antioxidants, mitochondrial respiratory chain, cardiolipin oxidation, reactive oxygen species, mitochondrial apoptosis, aging, age-related diseases, lifespan extension, H2O2-induced apoptosis, oxidative stress, mitochondrial reactive oxygen species
- MeSH terms
- Age Factors, Aging, Animals, Antioxidants, Electrophoresis, Humans, Mitochondria, Plastoquinone, Drug Delivery Systems, Apoptosis, Reactive Oxygen Species
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