1. Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation.
- Author
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Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, Gobierno de España, Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Junta de Andalucía, González Arzola, Katiuska, Díaz Quintana, Antonio Jesús, Bernardo García, Noelia, Martínez Fábregas, Jonathan, Rivero Rodríguez, Francisco, Casado Combreras, Miguel Ángel, Elena-Real, Carlos A., Velázquez Cruz, Alejandro, Gil Caballero, Sergio, Velázquez Campoy, Adrián, Szulc, Elzbieta, Gavilán Dorronzoro, María de la Paz, Ayala, Isabel, Arranz, Rocío, Ríos, Rosa M., Salvatella, Xavier, Valpuesta, José María, Hermoso, Juan A., Rosa Acosta, Miguel Ángel de la, Díaz Moreno, Irene, Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, Gobierno de España, Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Junta de Andalucía, González Arzola, Katiuska, Díaz Quintana, Antonio Jesús, Bernardo García, Noelia, Martínez Fábregas, Jonathan, Rivero Rodríguez, Francisco, Casado Combreras, Miguel Ángel, Elena-Real, Carlos A., Velázquez Cruz, Alejandro, Gil Caballero, Sergio, Velázquez Campoy, Adrián, Szulc, Elzbieta, Gavilán Dorronzoro, María de la Paz, Ayala, Isabel, Arranz, Rocío, Ríos, Rosa M., Salvatella, Xavier, Valpuesta, José María, Hermoso, Juan A., Rosa Acosta, Miguel Ángel de la, and Díaz Moreno, Irene more...
- Abstract
The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleolar liquid–liquid phase separation usually serves the cell as a fast, smart mechanism to control the spatial localization and trafcking of nuclear proteins. Actually, the alternative reading frame (ARF), a tumor suppressor protein sequestered by nucleophosmin (NPM) in the nucleoli, is shifted out from NPM upon DNA damage. DNA damage also triggers early translocation of respiratory Cc to nucleus before cytoplasmic caspase activation. Here, we show that Cc can bind to nucleolar NPM by triggering an extended-to-compact conformational change, driving ARF release. Such a NPM–Cc nucleolar interaction can be extended to a general mechanism for DNA damage in which the lysine-rich regions of Cc—rather than the canonical, arginine-rich stretches of membrane-less organelle components—controls the trafcking and availability of nucleolar proteins. more...
- Published
- 2022