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The Role of the Phosphate Carrier in the Ionophore Uncoupling Action of ω-Hydroxypalmitic Acid in Liver Mitochondria

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

Abstract

This paper examines the uncoupling effect of ω-hydroxypalmitic acid (HPA) on liver mitochondria energized by oxidation of succinate. It was shown that HPA more effectively stimulates respiration of mitochondria in the case of incubation in a medium containing potassium chloride, which indicates the ability of HPA to exert an ionophore effect on mitochondria associated with the transport of potassium and/or Tris ions into the matrix of organelles. It was suggested that the phosphate carrier of the inner mitochondrial membrane can be involved in the ionophore action of HPA. We have shown that inorganic phosphate (Pi), a phosphate carrier substrate, has a significant inhibitory effect on HPA-induced stimulation of respiration in liver mitochondria. In addition, Pi inhibits HPA-induced swelling of organelles caused by the transport of potassium and/or Tris ions into the mitochondrial matrix and also reduces the efficiency of HPA as an inducer of a decrease in the transmembrane potential (Δψ) of liver mitochondria. The inhibitors of the phosphate carrier, N-ethylmaleimide (NEM) and iminodi(methylene)phosphonate (IDMP), have a similar effect. It was shown that, upon stimulation of mitochondrial respiration by 30 μM HPA, the recoupling effects of Pi, NEM, and IDMP are 71 ± 8.3%, 56 ± 6.1%, and 34 ± 2.7%, respectively. Noteworthy, these ligands of the phosphate carrier have no effect on the protonophore effect of HPA. Thus, we conclude that the phosphate carrier of liver mitochondria takes part in the ionophore action of HPA, possibly facilitating the transfer of the HPA anion from the inner monolayer of the inner membrane to its outer monolayer.

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ACKNOWLEDGMENTS

The work was supported by the Russian Foundation for Basic Research (project no. 20-015-00124).

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Authors and Affiliations

  1. Mari State University, 424000, Yoshkar-Ola, Russia

    M. V. Dubinin, A. A. Semenova, O. E. Krasnoshchekova & V. N. Samartsev

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  1. M. V. Dubinin
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  2. A. A. Semenova
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  3. O. E. Krasnoshchekova
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  4. V. N. Samartsev
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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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Dubinin, M.V., Semenova, A.A., Krasnoshchekova, O.E. et al. The Role of the Phosphate Carrier in the Ionophore Uncoupling Action of ω-Hydroxypalmitic Acid in Liver Mitochondria. Biochem. Moscow Suppl. Ser. A 15, 348–355 (2021). https://doi.org/10.1134/S1990747821060039

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  • DOI: https://doi.org/10.1134/S1990747821060039

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