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

FEBS Lett. 2016 Sep;590(17):2836-43. doi: 10.1002/1873-3468.12319. Epub 2016 Aug 4.

Abstract

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/H2 O2 -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.

Keywords: antioxidant; binding; cardiolipin; cytochrome c; leakage; liposome.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism*
  • Antioxidants / pharmacology
  • Cardiolipins / biosynthesis*
  • Cytochromes c / biosynthesis*
  • Electron Transport / drug effects
  • Liposomes / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Oxidation-Reduction
  • Peroxidase / biosynthesis*
  • Plastoquinone / analogs & derivatives
  • Plastoquinone / pharmacology

Substances

  • 10-(6'-plastoquinonyl)decyltriphenylphosphonium
  • Antioxidants
  • Cardiolipins
  • Liposomes
  • Cytochromes c
  • Peroxidase
  • Plastoquinone