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ω-Hydroxypalmitic and α,ω-Hexadecanedioic Acids As Activators of Free Respiration and Inhibitors of H2O2 Generation in Liver Mitochondria

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

The effects of palmitic acid (PA) and the products of its ω-oxidation–ω-hydroxypalmitic acid (HPA) and α,ω-hexadecanedioic acid (HDA)—on respiration in the absence of ATP synthesis and on the H2O2 generation were studied on isolated liver mitochondria energized by oxidation of succinate. It was shown that HPA stimulates respiration and reduces the difference in electrical potentials (Δψ) in mitochondria to the same extent as is typical for PA and classical protonophore uncouplers. Under similar conditions, the stimulation of mitochondrial respiration by HDA is not accompanied by a decrease in Δψ and is suppressed by 10 μM cyclosporin A. In this regard, HDA is considered as a “decoupling” agent that switches the complexes of the mitochondrial respiratory chain to the idle mode. It was established that in the presence of 20 mM potassium chloride in the sucrose incubation medium, stimulation of respiration by HPA (in contrast to PA and HDA) is suppressed by 60% in the case of pre-incubation with 3 mM magnesium chloride. We found that under these conditions, HPA at a concentration of 25 μM and above induces mitochondrial swelling, which is completely suppressed by magnesium chloride. HPA as an inducer of mitochondrial swelling is less efficient in the absence of potassium chloride than in its presence. We assume that, in contrast to PA and HDA, HPA produces its activating influence on free respiration in mitochondria owing to a combination of its ionophore and protonophore effects. It was established that PA, HDA, and HPA in concentrations equally stimulating respiration of mitochondria in state 2 are equally efficient in inhibiting the H2O2 generation. We conclude that the effects of these fatty acids as inhibitors of H2O2 generation in isolated liver mitochondria are due to stimulation of respiration in various ways and are not associated with a decrease in Δψ.

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ACKNOWLEDGMENTS

This work was supported by the grant of the President of the Russian Federation for the state support of young Russian scientists (MK-61.2019.4).

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Authors and Affiliations

  1. Mari State University, 424001, Yoshkar-Ola, Russia

    A. A. Semenova, V. N. Samartsev, S. I. Pavlova & M. V. Dubinin

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  1. A. A. Semenova
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  2. V. N. Samartsev
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  3. S. I. Pavlova
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  4. M. V. Dubinin
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Correspondence to M. V. Dubinin.

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All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals. The Protocol of experiments was approved by the Commission on Bioethics of the Mari State University.

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Translated by M. Dubinin

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Semenova, A.A., Samartsev, V.N., Pavlova, S.I. et al. ω-Hydroxypalmitic and α,ω-Hexadecanedioic Acids As Activators of Free Respiration and Inhibitors of H2O2 Generation in Liver Mitochondria. Biochem. Moscow Suppl. Ser. A 14, 24–33 (2020). https://doi.org/10.1134/S1990747819060084

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