Involvement of the Mitochondrial Ca2+-Independent Phospholipase iPLA2 in the Induction of Mitochondrial Permeability Transition Pore by Long-Chain Acylcarnitines

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It is known that activated derivatives of long-chain fatty acids acylcarnitines (LCAC) are considered the most toxic, which, along with calcium, can participate in the induction of mitochondrial permeability transition pore, involving various types of phospholipases in the complex mechanisms of pore activation. In this work, we investigated the influence of different inhibitors of phospholipases and carnitine palmitoyltransferase-1 (CPT1) on the induction of mitochondrial permeability transition pore by D,L-palmitylcarnitine (PC, C16:0). In the experiments on isolated rat liver mitochondria, the effects of PC on mitochondrial respiration rate, mitochondrial potential (ΔΨm), and mitochondrial swelling were examined. It was shown that the application of the inhibitors of carnitine palmitoyltransferase-1 (Etomoxir 2), Ca2+-dependent phospholipase cPLA2 (Aristolochic acid), or Ca2+-independent phospholipase iPLA2γ ((R/S)-bromoenol lactone (BEL) and PACOCF3) caused an increase in the critical concentrations of D,L-palmitylcarnitine (PC*) required for ΔΨm dissipation and mitochondrial swelling. The most pronounced protective effect was caused by PACOCF3 and BEL. In state 3 of respiration (ADP + Mg2+ + hexokinase), Etomoxir 2 and Aristolochic acid enhanced respiration inhibition induced by excess D,L-palmitylcarnitine and promoted dissipation of ΔΨm, while-the inhibitors of iPLA2γ prevented the dissipation of ΔΨm evoked by D,L-palmitylcarnitine and caused an increase in the rate of mitochondrial respiration. Thus, the results obtained indicate the involvement of mitochondrial iPLA2γ in the induction of mitochondrial permeability transition pore by long-chain acylcarnitines.

Sobre autores

N. Fedotcheva

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: dynnik@rambler.ru
Russia, 142290, Moscow oblast, Pushchino

E. Grishina

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: dynnik@rambler.ru
Russia, 142290, Moscow oblast, Pushchino

V. Dynnik

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Autor responsável pela correspondência
Email: dynnik@rambler.ru
Russia, 142290, Moscow oblast, Pushchino

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