Post-Translational Nitration affects of Cytochrome c-Cardiolipin interaction

SANTIAGO OVIEDO ROUCO; DAIANA CAPDEVILA; DAMIAN ALVAREZ PAGGI; FLORENCIA TOMASINA; VERONICA DEMICHELI; RAFAEL RADI; DANIEL MURGIDA

Chascomus

Congreso; IV Latin American Meeting on Biological Inorganic Chemistry; 2014

Society of Biological Inorganic Chemistry

Cytochrome c (Cyt) is a multifunctional soluble hemoprotein: it behaves as mitochondrial electron carrier and as peroxidase enzyme in early events ofapoptosis. Mammalian Cyt contains four highly conserved Tyr residues at sequence positions 48, 67, 74 and 97. Under peroxynitrite challenge occurs nitration of solvent exposed Tyr74 or Tyr97.These modifications on Tyr74 induce deprotonation of this residue concomitant with the "alkaline transition" at neutral pH1 implying the detachment of the iron axial ligand Met80 and its replacement by lysine. It was shown that these alternative conformation present higher peroxidase activity. Based on these results, it has been proposed that nitration of Tyr74 may be implicated in oxidative sensing and early events of apoptosis.Besides the apoptotic function that Cyt exerts in the cytosol, Cyt acts as a specific cardiolipin-oxygenase to generate CL-OOH required for the release of proapoptotic factors into the cytosol2. However little is known about Cyt-CL complex for nitrated Cyt.In this work we study changes in conformation gated by nitration of Tyr74 and CL-Cyt complex formation.