title: Specific nitration of tyrosines 46 and 48 makes cytochrome c assemble a non-functional apoptosome.
abstract: Under nitroxidative stress, a minor fraction of cytochrome c can be modified by tyrosine nitration. Here we analyze the specific effect of nitration of tyrosines 46 and 48 on the dual role of cytochrome c in cell survival and cell death. Our findings reveal that nitration of these two solvent-exposed residues has a negligible effect on the rate of electron transfer from cytochrome c to cytochrome c oxidase, but impairs the ability of the heme protein to activate caspase-9 by assembling a non-functional apoptosome. It seems that cytochrome c nitration under cellular stress counteracts apoptosis in light of the small amount of modified protein. We conclude that other changes such as increased peroxidase activity prevail and allow the execution of apoptosis.
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, cicCartuja, Universidad de Sevilla-CSIC, Avda. Americo Vespucio 49, Sevilla 41092, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: García-Heredia
authors.forename: Irene
authors.initials: I
authors.lastname: Díaz-Moreno
authors.forename: Antonio
authors.initials: A
authors.lastname: Díaz-Quintana
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.forename: José A
authors.initials: JA
authors.lastname: Navarro
authors.forename: Manuel
authors.initials: M
authors.lastname: Hervás
authors.forename: Miguel A
authors.initials: MA
authors.lastname: De la Rosa
mesh_terms: D053478:Apoptosomes / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004579:Electron Transport / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015538:Nitrosation / Q000502:physiology*; D010084:Oxidation-Reduction; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D025941:Protein Interaction Mapping; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D053478:Apoptosomes; D050505:Mutant Proteins; D014443:Tyrosine; D045304:Cytochromes c; D020169:Caspases