Belosludtsev 2018 Biochim Biophys Acta

[[Has title::Belosludtsev KN, Belosludtseva NV, Talanov EY, Tenkov KS, Starinets VS, Agafonov AV, Pavlik LL, Dubinin MV (2018) Effect of bedaquiline on the functions of rat liver mitochondria. Biochim Biophys Acta [Epub ahead of print].]]

» [[Has info::PMID: 29920239]]

Belosludtsev KN, Belosludtseva NV, Talanov EY, Tenkov KS, Starinets VS, Agafonov AV, Pavlik LL, Dubinin MV (2018) Biochim Biophys Acta

Abstract: The paper considers the effects of bedaquiline (BDQ), an antituberculous preparation of the new generation, on rat liver mitochondria. It was shown that 50 μM BDQ inhibited mitochondrial respiration measured with substrates of complexes I and II (glutamate/malate and succinate/rotenone systems respectively) in the states V₃ and V_DNP. At the same time, at concentrations below 50 μM, 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 II + III of the mitochondrial transport chain. It was discovered that at concentrations up to 10 μM, BDQ inhibited H₂O₂ production in mitochondria. BDQ (10-50 μM) suppressed the opening of Ca²⁺-dependent CsA-sensitive mitochondrial permeability transition pore. The latter was revealed experimentally as the inhibition of Ca²⁺/P_i-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. • Keywords: Bedaquiline, K(+) transport, MPT pore, Mitochondria, Mitochondrial respiration, Oxidative phosphorylation • Bioblast editor: [[has editor::Plangger M]], [[has editor::Kandolf G]]

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 

Labels, 2018-08