Repositorio de producción científica de la Universidad de Sevilla

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

Opened Access Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

Citas

buscar en

Estadísticas
Icon
Exportar a
Autor: Moreno Beltrán, José Blas
Guerra Castellano, Alejandra
Díaz Quintana, Antonio Jesús
Conte, Rebecca del
García Mauriño, Sofía M.
González Arzola, Katiuska
Rosa Acosta, Miguel Ángel de la
Díaz Moreno, Irene
Departamento: Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
Fecha: 2017
Publicado en: Proceedings of the National Academy of Sciences, 114 (15), E3041-E3050.
Tipo de documento: Artículo
Resumen: Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methylL-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphoryla...
[Ver más]
Cita: Moreno Beltrán, J.B., Guerra Castellano, A., Díaz Quintana, A., Conte, R.d., García Mauriño, S.M., González Arzola, K.,...,Díaz Moreno, I. (2017). Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48. Proceedings of the National Academy of Sciences, 114 (15), E3041-E3050.
Tamaño: 1.968Mb
Formato: PDF

URI: http://hdl.handle.net/11441/68113

DOI: 10.1073/pnas.1618008114

Ver versión del editor

Mostrar el registro completo del ítem


Esta obra está bajo una Licencia Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internacional

Este registro aparece en las siguientes colecciones