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 SkQ1H2 from its oxidized form that appears as a result of the antioxidant activity of SkQ1H2. SkQ1H2 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 H2O2-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 mitochondriamediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast “biochemical suicide” of an organism after a severe metabolic crisis.
Keywords: Electric potential difference, mitochondria, drug targeting, antioxidant, plastoquinone, ischemia/reperfusion, kidney, rhabdomyolysis, cataract, retinopathies
Current Drug Targets
Title: Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies
Volume: 12 Issue: 6
Author(s): V. A. Roginsky, V. P. Skulachev, D. B. Zorov, A. A. Zamyatnin, M. Y. Vyssokikh, K. M. Shidlovsky, V. N. Tashlitsky, T. P. Shkurat, F. F. Severin, I. I. Severina, A. Y. Savchenko, M. V. Skulachev, E. Y. Plotnikov, K. G. Lyamzaev, G. A. Korshunova, N. G. Kolosova, M. V. Egorov, V. A. Chistyakov, D. A. Cherepanov, B. V. Chernyak, V. N. Anisimov and Y. N. Antonenko
Affiliation:
Keywords: Electric potential difference, mitochondria, drug targeting, antioxidant, plastoquinone, ischemia/reperfusion, kidney, rhabdomyolysis, cataract, retinopathies
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 SkQ1H2 from its oxidized form that appears as a result of the antioxidant activity of SkQ1H2. SkQ1H2 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 H2O2-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 mitochondriamediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast “biochemical suicide” of an organism after a severe metabolic crisis.
Export Options
About this article
Cite this article as:
A. Roginsky V., P. Skulachev V., B. Zorov D., A. Zamyatnin A., Y. Vyssokikh M., M. Shidlovsky K., N. Tashlitsky V., P. Shkurat T., F. Severin F., I. Severina I., Y. Savchenko A., V. Skulachev M., Y. Plotnikov E., G. Lyamzaev K., A. Korshunova G., G. Kolosova N., V. Egorov M., A. Chistyakov V., A. Cherepanov D., V. Chernyak B., N. Anisimov V. and N. Antonenko Y., Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies, Current Drug Targets 2011; 12 (6) . https://dx.doi.org/10.2174/138945011795528859
DOI https://dx.doi.org/10.2174/138945011795528859 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Multimodality Imaging in Acute Ischemic Stroke
Current Medical Imaging Effects of Erythropoietin on Brain Function
Current Pharmaceutical Biotechnology Alveolar Capillary Dysplasia: A Lethal Developmental Lung Malformation
Current Respiratory Medicine Reviews Melatonin, Autophagy and Intestinal Bowel Disease
Current Pharmaceutical Design Cytoprotection by Natural and Synthetic Polyphenols in the Heart: Novel Mechanisms and Perspectives
Current Pharmaceutical Design Stem Cells in Stroke Repair: Current Success & Future Prospects
CNS & Neurological Disorders - Drug Targets Modulation of Neuro-Inflammation and Vascular Response by Oxidative Stress Following Cerebral Ischemia-Reperfusion Injury
Current Medicinal Chemistry Plasticity in Uterine Innervation: State of the Art
Current Protein & Peptide Science Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde
Current Cancer Drug Targets Multivalent & Multifunctional Ligands to β-Amyloid
Current Pharmaceutical Design Activators of Sirtuin-1 and their Involvement in Cardioprotection
Current Medicinal Chemistry Appraisal of Nano-Lipidic Astaxanthin cum Thermoreversible Gel and its Efficacy in Haloperidol Induced Parkinsonism
Current Drug Delivery Modulation of Individual Susceptibility to the No-Reflow Phenomenon after Acute Myocardial Infarction
Current Pharmaceutical Design Involvement of Leukotriene Pathway in the Pathogenesis of Ischemia- Reperfusion Injury and Septic and Non-Septic Shock
Current Vascular Pharmacology Sepsis and Solid Organ Transplantation
Current Drug Targets Cyclooxygenase-2 Inhibition and Side-effects of Non-steroidal Antiinflammatory Drugs in the Gastrointestinal Tract.
Current Medicinal Chemistry Curcumin: Not So Spicy After All
Mini-Reviews in Medicinal Chemistry Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome
Current Pediatric Reviews Antiinflammatory Activity of Melatonin in Central Nervous System
Current Neuropharmacology Traditional Fruits of Kerala: Bioactive Compounds and their Curative Potential in Chronic Diseases
Current Nutrition & Food Science