Cited by 156Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsCoenzyme Q10 studies and effects

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Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies

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.·2011·Current Drug Targets

DOI 10.2174/138945011795528859

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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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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)
DOI: 10.2174/138945011795528859
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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Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies

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