Belosludtseva 2022 Membranes (Basel)

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Belosludtseva NV, Pavlik LL, Belosludtsev KN, Saris NL, Shigaeva MI, Mironova GD (2022) The short-term opening of cyclosporin A-independent palmitate/Sr 2+-induced pore can underlie ion efflux in the oscillatory mode of functioning of rat liver mitochondria.

Β» Membranes (Basel) 12:667. PMID: 35877870 Open Access

Belosludtseva Natalia V, Pavlik Lyubov L, Belosludtsev Konstantin N, Saris Nils-Erik L, Shigaeva Maria I, Mironova Galina D (2022) Membranes (Basel)

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. β€’ Keywords: Cyclosporin A, Cyclosporin A-independent palmitate/Ca2+-induced permeability transition pore, Ion oscillations, Lipid pore, Mitochondria, Mitochondrial permeability transition, Palmitic acid, Phospholipase A2 β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: RU Pushchino Mironova GD

Labels: MiParea: Respiration 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 

HRR: Oxygraph-2k, O2k-Fluorometer 

2022-08, AmR 

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