Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid–liquid phase separation | Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation.
2022
González-Arzola, Katiuska | Díaz-Quintana, Antonio | Bernardo-García, Noelia | Martínez-Fábregas, Jonathan | Rivero-Rodríguez, Francisco | Casado-Combreras, Miguel Á | Elena-Real, Carlos | Velázquez-Cruz, Alejandro | Gil-Caballero, Sergio | Velázquez-Campoy, Adrián | Szulc, Elzbieta | Gavilán, María | Ayala, Isabel | Arranz, Rocío | Ríos, Rosa | Salvatella, Xavier | Valpuesta, José | Hermoso, Juan | de la Rosa, Miguel | Díaz-Moreno, Irene | Universidad de Sevilla = University of Seville | Université Paris-Saclay | Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Instituto de Química Física Rocasolano = Instituto de Química Física Blas Cabrera = Institute of Physical Chemistry Rocasolano (IQFR) ; Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain] (CSIC) | Institut de biologie structurale (IBS - UMR 5075) ; Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA) | Instituto de Biocomputación y Física de Sistemas Complejos = Institute for Biocomputation and Physics of Complex Systems (BIFI) ; Universidad de Zaragoza = University of Zaragoza [Saragossa University] = Université de Saragosse | Universidad de Zaragoza = University of Zaragoza [Saragossa University] = Université de Saragosse | Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón) ; Universidad de Zaragoza = University of Zaragoza [Saragossa University] = Université de Saragosse | Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas = Biomedical Research Network Center for Liver and Digestive Diseases [Madrid] (CIBERehd) | Fundación Agencia Aragonesa para la Investigación y el Desarrollo = Aragonese Foundation for Research & Development (ARAID) | Institute for Research in Biomedicine [Barcelona, Spain] (IRB) ; Universitat de Barcelona (UB)-Barcelona Institute of Science and Technology (BIST) | Centro Andaluz de Biología Molecular y Medicina Regenerativa = Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER) | Centro Nacional de Biotecnología [Madrid] (CNB-CSIC) ; Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain] (CSIC) | Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies (ICREA) | Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain] (CSIC) | Horizon 2020 program of the European Commission,Cámara Foundation (C.A.E.R.´s fellowship) | European Regional Development Fund Regional Development Fund (FEDER) | European Project: 648201,H2020,ERC-2014-CoG,CONCERT(2015)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. 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 trafficking 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 trafficking and availability of nucleolar proteins.
اظهر المزيد [+] اقل [-]المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique