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

• Published in: Biochemistry (Moscow) 2013-04, Vol.78 (4), p.412-417
• Main Authors: Dubinin, M. V., Adakeeva, S. I., Samartsev, V. N.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Calcium - analysis; Calcium - metabolism; Calcium ions; Carboxylic acids; Cyclosporine - pharmacology; Dicarboxylic Acids - chemistry; Dicarboxylic Acids - metabolism; Dicarboxylic Acids - pharmacology; Dose-Response Relationship, Drug; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Ions - antagonists & inhibitors; Ions - metabolism; Life Sciences; Male; Microbiology; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Oxidation-reduction reaction; Permeability - drug effects; Rats; Ruthenium Red - pharmacology; Strontium - analysis; Strontium - metabolism; Structure-Activity Relationship
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S000629791304010X

Long-chain saturated monocarboxylic fatty acids can induce nonspecific permeability of the inner membrane (open pores) of liver mitochondria loaded with Ca 2+ or Sr 2+ 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 Ca 2+ or Sr 2+ leads to swelling of the organelles and release of these ions from the matrix. The maximum effect of HDA is observed at 50 μM Ca 2+ 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 Ca 2+ and Sr 2+ 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 Ca 2+ or Sr 2+ 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.