Post-Translational Nitration Affects Cytochrome c-Cardiolipin Interactions

OVIEDO ROUCO, SANTIAGO; CAPDEVILA, DAIANA A.; DEMICHELI, VERÓNICA; TOMASINA, FLORENCIA; TÓRTORA, VERÓNICA; RADI, RAFAEL; MURGIDA, DANIEL H.

Chascomúas

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

SBIC

Cytochrome c (Cyt) is a multifunctional soluble hemoprotein that behaves bothas mitochondrial electron carrier and as a proapoptotic factor. Mammalian Cyt contains four highly conserved Tyr residues at sequence positions 48, 67, 74 and 97. Under peroxynitrite challenge solvent exposed Tyr74 or Tyr97 are nitrated. Nitration ofTyr74inducesdeprotonation of this residue concomitant with an early "alkaline transition" that implies the replacement of the iron axial ligand Met80 by a lysine residue1. The alternative conformation presents increased peroxidase activity.Based on these results, it has been proposed that nitration of Tyr74 may be implicated in oxidative sensing and in the permeabilization of the mithocondrial membraneduring the early events of apoptosis.Specifically it has been shown that Cyt acts as a cardiolipin-oxygenase to generate CL-OOH, thus favoring the release of proapoptoticfactors into the cytosol2.The interactions of nitrated Cyt with CL, however, are less clear. Here we present a spectroscopic study of the conformational changes triggered by Tyr74 nitration and by interactions of the nitrated protein with CL.