The Short-Term Opening of Cyclosporin A-Independent Palmitate/Sr2+-Induced Pore Can Underlie Ion Efflux in the Oscillatory Mode of Functioning of Rat Liver Mitochondria

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Belosludtseva, N.V.; Pavlik, L.L.; Belosludtsev, K.N.; Saris, N.-E.L.; Shigaeva, M.I.; Mironova, G.D. The Short-Term Opening of Cyclosporin A-Independent Palmitate/Sr2+-Induced Pore Can Underlie Ion Efflux in the Oscillatory Mode of Functioning of Rat Liver Mitochondria. Membranes 2022, 12, 667.

Title: The Short-Term Opening of Cyclosporin A-Independent Palmitate/Sr2+-Induced Pore Can Underlie Ion Efflux in the Oscillatory Mode of Functioning of Rat Liver Mitochondria
Author: Belosludtseva, Natalia V.; Pavlik, Lyubov L.; Belosludtsev, Konstantin N.; Saris, Nils-Erik L.; Shigaeva, Maria I.; Mironova, Galina D.
Publisher: Multidisciplinary Digital Publishing Institute
Date: 2022-06-28
URI: http://hdl.handle.net/10138/346018
Abstract: Mitochondria are capable of synchronized oscillations in many variables, but the underlying mechanisms are still unclear. In this study, we demonstrated that rat liver mitochondria, when exposed to a pulse of Sr<sup>2+</sup> ions in the presence of valinomycin (a potassium ionophore) and cyclosporin A (a specific inhibitor of the permeability transition pore complex) under hypotonia, showed prolonged oscillations in K<sup>+</sup> and Sr<sup>2+</sup> fluxes, membrane potential, pH, matrix volume, rates of oxygen consumption and H<sub>2</sub>O<sub>2</sub> formation. The dynamic changes in the rate of H<sub>2</sub>O<sub>2</sub> production were in a reciprocal relationship with the respiration rate and in a direct relationship with the mitochondrial membrane potential and other indicators studied. The pre-incubation of mitochondria with Ca<sup>2+</sup>(Sr<sup>2+</sup>)-dependent phospholipase A<sub>2</sub> inhibitors considerably suppressed the accumulation of free fatty acids, including palmitic and stearic acids, and all spontaneous Sr<sup>2+</sup>-induced cyclic changes. These data suggest that the mechanism of ion efflux from mitochondria is related to the opening of short-living pores, which can be caused by the formation of complexes between Sr<sup>2+</sup>(Ca<sup>2+</sup>) and endogenous long-chain saturated fatty acids (mainly, palmitic acid) that accumulate due to the activation of phospholipase A<sub>2</sub> by the ions. A possible role for transient palmitate/Ca<sup>2+</sup>(Sr<sup>2+</sup>)-induced pores in the maintenance of ion homeostasis and the prevention of calcium overload in mitochondria under pathophysiological conditions is discussed.


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