Mitochondria-targeted 1,4-naphthoquinone (SkQN) is a powerful prooxidant and cytotoxic agent.

Autor: Goleva TN; Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Russian Federation., Lyamzaev KG; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation., Rogov AG; Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Russian Federation., Khailova LS; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation., Epremyan KK; Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Russian Federation., Shumakovich GP; Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Russian Federation., Domnina LV; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation., Ivanova OY; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation., Marmiy NV; Faculty of Biology, Institute of Mitoengineering, M.V. Lomonosov Moscow State University, Russian Federation., Zinevich TV; Faculty of Biology, Institute of Mitoengineering, M.V. Lomonosov Moscow State University, Russian Federation., Esipov DS; Faculty of Biology, Institute of Mitoengineering, M.V. Lomonosov Moscow State University, Russian Federation., Zvyagilskaya RA; Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Russian Federation., Skulachev VP; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation., Chernyak BV; A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation. Electronic address: bchernyak1@gmail.com.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Bioenergetics [Biochim Biophys Acta Bioenerg] 2020 Aug 01; Vol. 1861 (8), pp. 148210. Date of Electronic Publication: 2020 Apr 17.
DOI: 10.1016/j.bbabio.2020.148210
Abstrakt: An increase in the production of reactive oxygen species (ROS) in mitochondria due to targeted delivery of redox active compounds may be useful in studies of modulation of cell functions by mitochondrial ROS. Recently, the mitochondria-targeted derivative of menadione (MitoK 3 ) was synthesized. However, MitoK 3 did not induce mitochondrial ROS production and lipid peroxidation while exerting significant cytotoxic action. Here we synthesized 1,4-naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) as a prototype of mitochondria-targeted prooxidant, and its redox properties, interactions with isolated mitochondria, yeast cells and various human cell lines were investigated. According to electrochemical measurements, SkQN was more active redox agent and, due to the absence of methyl group in the naphthoquinone ring, more reactive as electrophile than MitoK 3 . SkQN (but not MitoK 3 ) stimulated hydrogen peroxide production in isolated mitochondria. At low concentrations, SkQN stimulated state 4 respiration in mitochondria, decreased membrane potential, and blocked ATP synthesis, being more efficient uncoupler of oxidative phosphorylation than MitoK 3 . In yeast cells, SkQN decreased cell viability and induced oxidative stress and mitochondrial fragmentation. SkQN killed various tumor cells much more efficiently than MitoK 3 . Since many tumors are characterized by increased oxidative stress, the use of new mitochondria-targeted prooxidants may be a promising strategy for anticancer therapy.
Competing Interests: Declaration of competing interest We declare that i) the manuscript, or part of it, have neither been published nor are currently under consideration for publication by any other journal. We further declare that we have read the manuscript and approved its submission to BBA Bioenergetics. We also wish to confirm that there are no conflicts of interest associated with this publication.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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