Belosludtsev 2019 Biochim Biophys Acta Biomembr
Belosludtsev KN, Belosludtseva NV, Talanov EY, Tenkov KS, Starinets VS, Agafonov AV, Pavlik LL, Dubinin MV (2019) Effect of bedaquiline on the functions of rat liver mitochondria. Biochim Biophys Acta Biomembr 1861:288-97. |
Belosludtsev KN, Belosludtseva NV, Talanov EY, Tenkov KS, Starinets VS, Agafonov AV, Pavlik LL, Dubinin MV (2019) Biochim Biophys Acta Biomembr
Abstract: The paper considers the effects of bedaquiline (BDQ), an antituberculous preparation of the new generation, on rat liver mitochondria. It was shown that 50β―ΞΌM BDQ inhibited mitochondrial respiration measured with substrates of complexes I and II (glutamate/malate and succinate/rotenone systems respectively) in the states V3 and VDNP. At the same time, at concentrations below 50β―ΞΌM, BDQ slightly stimulated respiration with substrates of complex I in the state V2. BDQ was also found to suppress, in a dose-dependent manner, the activity of complex II and the total activity of complexes IIβ―+β―III of the mitochondrial transport chain. It was discovered that at concentrations up to 10β―ΞΌM, BDQ inhibited H2O2 production in mitochondria. BDQ (10-50β―ΞΌM) suppressed the opening of Ca2+-dependent CsA-sensitive mitochondrial permeability transition pore. The latter was revealed experimentally as the inhibition of Ca2+/Pi-dependent swelling of mitochondria, suppression of cytochrome c release, and an increase in the Ca2+ capacity of the organelles. BDQ also decreased the rate of mitochondrial energy-dependent K+ transport, which was evaluated by the energy-dependent swelling of mitochondria in a K+ buffer and DNP-induced K+ efflux from the organelles. The possible mechanisms of BDQ effect of rat liver mitochondria are discussed.
Copyright Β© 2018 Elsevier B.V. All rights reserved. β’ Keywords: Bedaquiline, K(+) transport, MPT pore, Mitochondria, Mitochondrial respiration, Oxidative phosphorylation β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Rat
Tissue;cell: Liver
Preparation: Isolated mitochondria
Regulation: Ion;substrate transport, Uncoupler Coupling state: LEAK, OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k
Labels, 2019-07