A mitochondria‐targeted antioxidant can inhibit peroxidase activity of cytochrome c by detachment of the protein from liposomes

Interaction of cytochrome c with cardiolipin converts this respiratory chain electron‐transfer protein into a peroxidase, supposedly involved in mitochondria‐mediated apoptosis initiation. Liposome membrane permeabilization provoked by peroxidase activity of the cytochrome c /cardiolipin complex has been previously shown to be suppressed by conventional antioxidants. Here, the mitochondria‐targeted antioxidant SkQ1 (plastoquinonyl‐decyl‐triphenylphosphonium) was found to strongly inhibit both cytochrome c /cardiolipin peroxidase activity and the permeabilization of liposomes composed of phosphatidylcholine and cardiolipin. A number of binding assays revealed a significant inhibiting effect of SkQ1 on cytochrome c binding to liposomes, thus suggesting that SkQ1‐mediated protection of liposomes from the cytochrome c /H 2 O 2 ‐induced permeabilization involved distortion of the cytochrome c ‐membrane binding. It is suggested that antioxidant and antiapoptotic effects of alkyltriphenylphosphonium cations can be related to the prevention of cytochrome c /cardiolipin interaction.