Long-Chain α,ω-Dioic Acids as Inducers of Cyclosporin A-Insensitive Nonspecific Permeability of the Inner Membrane of Liver Mitochondria Loaded with Calcium or Strontium Ions

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M. V. Dubinin, S. I. Adakeeva, and V. N. Samartsev^*

Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia; fax: (8362) 56-5781; E-mail: samvic56@mail.ru

^* To whom correspondence should be addressed.

Received July 23, 2012; Revision received October 31, 2012

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Long-chain saturated monocarboxylic fatty acids can induce nonspecific permeability of the inner membrane (open pores) of liver mitochondria loaded with Ca²⁺ or Sr²⁺ by the mechanism insensitive to cyclosporin A. In this work we investigated the effect of their metabolites – α,ω-dioic (dicarboxylic) acids – as potential inducers of pore opening by a similar mechanism. It was established that the addition of α,ω-hexadecanedioic acid (HDA) at a concentration of 10-30 µM to liver mitochondria loaded with Ca²⁺ or Sr²⁺ leads to swelling of the organelles and release of these ions from the matrix. The maximum effect of HDA is observed at 50 µM Ca²⁺ concentration. Cyclosporin A at a concentration of 1 µM, previously added to the mitochondria, did not inhibit the observed processes. The calcium uniporter inhibitor ruthenium red, which blocks influx of Ca²⁺ and Sr²⁺ to the matrix of mitochondria, prevented HDA-induced swelling. The effect of HDA as inducer of swelling of mitochondria was compared with similar effects of α,ω-tetradecanedioic and α,ω-dodecanedioic acids whose acyl chains are two and four carbon atoms shorter than HDA, respectively. It was found that the efficiency of these α,ω-dioic acids decreases with reducing number of carbon atoms in their acyl chains. It was concluded that in the presence of Ca²⁺ or Sr²⁺ long-chain saturated α,ω-dioic acids can induce a cyclosporin A-insensitive permeability of the inner membrane (open pores) of liver mitochondria as well as their monocarboxylic analogs.

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KEY WORDS: liver mitochondria, α,ω-dioic acid, cyclosporin A-insensitive pore, calcium ions

DOI: 10.1134/S000629791304010X

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