ИСТИНА

Interaction of cytochrome c with mitochondrial cardiolipin is known to convert this electron transfer protein into peroxidase, which is supposed to play an essential role in apoptosis. Cytochrome c/cardiolipin peroxidase activity has been found previously to cause permeabilization of liposome membranes, in particular, leakage of fluorescent probes, such as carboxyfluorescein, sulforhodamine B and 3-kDa (but not 10-kDa) fluorescent dextran from liposomes. The liposome leakage induced by horse heart cytochrome c in the presence of hydrogen peroxide has appeared to be sensitive to the inhibiting action of antioxidants, such as trolox and quercetin. Here we studied the effect of the mitochondria-targeted antioxidant SkQ1 on the cytochrome c/cardiolipin peroxidase activity as measured by leakage of calcein from liposomes. The addition of SkQ1 at a low concentration (less than 50 nM) suppressed the liposome leakage induced by the combination of cytochrome c and H2O2. The inhibiting effect was also observed with dodecyl-triphenylphosphonium (C12TPP), the analog of SkQ1 lacking the plastoquinone moiety. SkQ1 was more effective in suppression the cytochrome c/H2O2-induced membrane permeabilization than C12TPP. Surprisingly, the inhibition by SkQ1 was independent of its redox state. Differential scanning calorimetry (DSC) measurements revealed a decrease in cytochrome c binding to lipid membranes, which could be considered as a mechanism of the SkQ1 effect on the cytochrome c/cardiolipin peroxidase activity.