A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+

The article examines the molecular mechanism of the Ca2+-dependent cyclosporin A (CsA)-insensitive permeability transition in rat liver mitochondria induced by alpha,omega-dioic acids. The addition of alpha,omega-hexadecanedioic acid (HDA) to Ca2+-loaded liver mitochondria was shown to induce a high-amplitude swelling of the organelles, a drop of membrane potential and the release of Ca2+ from the matrix, the effects being insensitive to CsA. The experiments with liposomes loaded with sulforhodamine B (SRB) revealed that, like palmitic acid (PA), HDA was able to cause permeabilization of liposomal membranes. However, the kinetics of HDA- and PA-induced release of SRB from liposomes was different, and HDA was less effective than PA in the induction of SRB release. Using the method of ultrasound interferometry, we also showed that the addition of Ca2+ to HDA-containing liposomes did not change the phase state of liposomal membranes-in contrast to what was observed when Ca2+ was added to PA-containing vesicles. It was suggested that HDA/Ca2+- and PA/Ca2+-induced permeability transition occurs by different mechanisms. Using the method of dynamic light scattering, we further revealed that the addition of Ca2+ to HDA-containing liposomes induced their aggregation/fusion. Apparently, these processes result in a partial release of SRB due to the formation of fusion pores. The possibility that this mechanism underlies the HDA/Ca2+-induced permeability transition of the mitochondrial membrane is discussed.