A Comparative Study of the Effects of Palmitic Acid and ω-Hydroxypalmitic Acid as Inducers of Ca²⁺-Dependent Permeabilization of Liver Mitochondria and Lecithin Liposomes

Abstract

The effects of ω-hydroxypalmitic acid as an inducer of Ca²⁺-dependent membrane permeabilization were studied on isolated rat liver mitochondria energized by succinate oxidation and lecithin liposomes. These Ca²⁺-dependent effects of ω-hydroxypalmitic acid on mitochondria and liposomes were compared with similar well-studied effects of palmitic acid. It was found that ω-hydroxypalmitic acid induced significantly more intensive mitochondrial swelling than palmitic acid in the presence of cyclosporin A and, therefore, was a more effective inducer of Ca²⁺-dependent cyclosporin A-insensitive permeabilization of the inner membrane of the organelles. At the same time, ω-hydroxypalmitic acid was a much less effective inducer of Ca²⁺-dependent release of sulforhodamine B from liposomes compared to palmitic acid. It has been shown that, in contrast to palmitic acid, the action of ω-hydroxypalmitic acid as an inducer of Ca²⁺-dependent pore in the liver mitochondria was completely blocked by inorganic phosphate in the presence of cyclosporin A. It was found that in this case inorganic phosphate cannot be replaced by vanadate, a permeable anion with similar properties. These results are considered as evidence of significant difference in the mechanisms of action of ω-hydroxypalmitic acid and palmitic acid as inducers of the Ca²⁺-dependent permeabilization of liver mitochondria. While the Ca²⁺-dependent effect of palmitic acid can be considered to be due the formation of a lipid pore, the Ca²⁺-dependent effect of ω-hydroxypalmitic acid in the presence of inorganic phosphate can be due to the formation of a cyclosporin A-sensitive mitochondrial permeability transition pore. The effect of inorganic phosphate as an inhibitor of ω-hydroxypalmitic acid-induced Ca²⁺-dependent cyclosporin A-sensitive pore in liver mitochondria is discussed.