Membranotropic effects of ω-hydroxypalmitic acid and Ca2+ on rat liver mitochondria and lecithin liposomes. Aggregation and membrane permeabilization

The paper examines membranotropic Ca 2+ -dependent effects of ω-hydroxypalmitic acid (HPA), a product of ω-oxidation of fatty acids, on the isolated rat liver mitochondria and artificial membrane systems (liposomes). It was established that in the presence of Ca 2+ , HPA induced aggregation of liver mitochondria, which was accompanied by the release of cytochrome c from the organelles. It was further demonstrated that the addition of Ca 2+ to HPA-containing liposomes induced their aggregation and/or fusion. Ca 2+ also caused the release of the fluorescent dye sulforhodamine B from liposomes, indicating their permeabilization. HPA was shown to induce a high-amplitude swelling of Ca 2+ -loaded mitochondria, to decrease their membrane potential, to induce the release of Ca 2+ from the organelles and to result in the oxidation of the mitochondrial NAD(P)H pool. Those effects of HPA were not blocked by the MPT pore inhibitor CsA, but were suppressed by the mitochondrial calcium uniporter inhibitor ruthenium red. The effects of HPA were also observed when Ca 2+ was replaced with Sr 2+ (but not with Ba 2+ or Mg 2+ ). A supposition is made that HPA can induce a Ca 2+ -dependent aggregation of mitochondria, as well as Ca 2+ dependent CsA-insensitive permeabilization of the inner mitochondrial membrane – with the subsequent lysis of the organelles.