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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.

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 Sr²⁺ 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⁺ and Sr²⁺ fluxes, membrane potential, pH, matrix volume, rates of oxygen consumption and H₂O₂ formation. The dynamic changes in the rate of H₂O₂ 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 Ca²⁺(Sr²⁺)-dependent phospholipase A₂ inhibitors considerably suppressed the accumulation of free fatty acids, including palmitic and stearic acids, and all spontaneous Sr²⁺-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 Sr²⁺(Ca²⁺) and endogenous long-chain saturated fatty acids (mainly, palmitic acid) that accumulate due to the activation of phospholipase A₂ by the ions. A possible role for transient palmitate/Ca²⁺(Sr²⁺)-induced pores in the maintenance of ion homeostasis and the prevention of calcium overload in mitochondria under pathophysiological conditions is discussed.

SUBMITTER: Belosludtseva NV

PROVIDER: S-EPMC9319229 | biostudies-literature |

REPOSITORIES: biostudies-literature

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