dc.creator | Guerra Castellano, Alejandra | es |
dc.creator | Díaz Quintana, Antonio Jesús | es |
dc.creator | Pérez Mejías, Gonzalo | es |
dc.creator | Elena-Real, Carlos A. | es |
dc.creator | González Arzola, Katiuska | es |
dc.creator | García Mauriño, Sofía M. | es |
dc.creator | Rosa Acosta, Miguel Ángel de la | es |
dc.creator | Díaz Moreno, Irene | es |
dc.date.accessioned | 2018-08-29T08:49:20Z | |
dc.date.available | 2018-08-29T08:49:20Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Guerra Castellano, A., Díaz Quintana, A.J., Pérez Mejías, G., Elena-Real, C.A., González Arzola, K., García Mauriño, S.M.,...,Díaz Moreno, I. (2018). Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria. Proceedings of the National Academy of Sciences, 115 (31), 7955-7960. | |
dc.identifier.issn | 1091-6490 | es |
dc.identifier.uri | https://hdl.handle.net/11441/78277 | |
dc.description.abstract | Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p-carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c, but significantly affects the entire oxidative phosphorylation process. In fact, the electron donation rate of the mutant heme protein to cytochrome c oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome c with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome c also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial metabolism in acute diseases, such as brain ischemia, and thus could allow the use of phosphomimetic cytochrome c as a neuroprotector with therapeutic applications. | es |
dc.description.sponsorship | España, Junta de Andalucía BIO-198 | es |
dc.description.sponsorship | España MINECO BFU2015-71017/BMC | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | National Academy of Sciences | es |
dc.relation.ispartof | Proceedings of the National Academy of Sciences, 115 (31), 7955-7960. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | cytochrome c | es |
dc.subject | electron transport chain | es |
dc.subject | oxidative stress | es |
dc.subject | phosphorylation | es |
dc.subject | reactive oxygen species | es |
dc.title | Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | BFU2015-71017/BMC | es |
dc.relation.projectID | BIO-198 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1073/pnas.1806833115 | es |
dc.identifier.doi | 10.1073/pnas.1806833115 | es |
idus.format.extent | 5 p. | es |
dc.journaltitle | Proceedings of the National Academy of Sciences | es |
dc.publication.volumen | 115 | es |
dc.publication.issue | 31 | es |
dc.publication.initialPage | 7955 | es |
dc.publication.endPage | 7960 | es |
dc.contributor.funder | Junta de Andalucía | |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | |