HYDROGEN PEROXIDE-INUDUCED GAIN OF PEROXIDASE ACTIVITYOF CYTOCHROME C UPON PHOSPHATE-MEDIATED BINDING TO ZWITTERIONIC LIPIDS: IMPLICATIONS FOR APOPTOSIS

DAIANA ANDREA CAPDEVILA; FLORENCIA TOMASINA; WALDEMAR MARMISOLLÉ; VERONICA DEMICHELI; RAFAEL RADI; DANIEL MURGIDA

Paris

Congreso; FEBS (Federation of European Biochemical Societies) EMBO (Excellence in life sciences) 2014 Conference; 2014

Federation of European Biochemical Societies

Cytochrome c (Cyt-c) has been shown to participate in cardiolipin (CL) oxidation and, therefore, in mitochondrial membranepermeabilization during the early events of apoptosis. The gain of peroxidatic activity has been ascribed to CL/Cyt-c interactionswhich, nevertheless, are also ubiquitous in healthy cells, thereby posing the question of which is the triggering event.We observed that the cationic protein Cyt-c is able to interact electrostatically with the main lipid components of the mitochondrialmembranes, the zwitterionic lipids phosphatidylcholine and phosphatidylethanolamine, through mediating phosphate anions thatinteract specifically with amino groups in the surfaces of the protein and the membrane models1. We have investigated the chemicalreactivity of Cytc- associated to model systems and in complexes with PE- and PC-liposomes using a combination ofelectrochemistry, Raman, fluorescence and mass spectroscopy. In these complexes Cyt-c reacts efficiently with H2O2 at submillimolarlevels, which specifically sulphoxides the axial ligand Met80 (SO-Cyt). The modified protein is stable and presents significantlyenhanced peroxidatic activity.