The Short-Term Opening of Cyclosporin A-Independent Palmitate/Sr[sup.2+]-Induced Pore Can Underlie Ion Efflux in the Oscillatory Mode of Functioning of Rat Liver Mitochondria

• Published in: Membranes (Basel) 2022-06, Vol.12 (7)
• Main Authors: Belosludtseva, Natalia V, Pavlik, Lyubov L, Belosludtsev, Konstantin N, Saris, Nils-Erik L, Shigaeva, Maria I, Mironova, Galina D
• Format: Article
• Language: English
• Subjects: Analysis; Cyclosporine; Dosage and administration; Membranes (Biology); Mitochondria; Physiological aspects; Physiology, Pathological
• ISSN: 2077-0375; 2077-0375
• DOI: 10.3390/membranes12070667

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+] 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.+] and Sr[sup.2+] fluxes, membrane potential, pH, matrix volume, rates of oxygen consumption and H[sub.2]O[sub.2] formation. The dynamic changes in the rate of H[sub.2]O[sub.2] 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+](Sr[sup.2+])-dependent phospholipase A[sub.2] inhibitors considerably suppressed the accumulation of free fatty acids, including palmitic and stearic acids, and all spontaneous Sr[sup.2+]-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+](Ca[sup.2+]) and endogenous long-chain saturated fatty acids (mainly, palmitic acid) that accumulate due to the activation of phospholipase A[sub.2] by the ions. A possible role for transient palmitate/Ca[sup.2+](Sr[sup.2+])-induced pores in the maintenance of ion homeostasis and the prevention of calcium overload in mitochondria under pathophysiological conditions is discussed.