Objectif "Mitochondrial respiratory chain complexes assemble from nuclear- and mitochondria-encoded subunits in the inner membrane. To protect cells from accumulating unassembled subunits in the membrane, ROS generation, or damage of mitochondrial integrity, regulatory mechanisms to balance and control the fidelity of the assembly process have evolved, encorporating a retention system enabling the preservation of a select few founding complexes for on-demand assembly. In yeast mitochondria, a feedback mechanism has been identified for the cytochrome oxidase in which assembly-intermediates specifically inactivate translation of the core subunit Cox1. It is controversially debated if similar translation regulating mechanisms exist in human mitochondria. However, our recent findings show that in human mitochondria assembly intermediates of respiratory chain complexes affect translation, nevertheless the underlying sensing and signalling mechanisms as well as the protein components appear to be more complex than in yeast. We aim to understand how this regulatory cycle is established; how does a distinct assembly intermediate of cytochrome oxidase signal the translation system, and how the influx of imported subunits contributes to this process. These goals are conceptually deeply rooted in a comprehensive understanding of the membrane protein complex assembly process and the factors that promote its progression. These objectives are of key importance for understanding the molecular pathology of mitochondrial encephalomyopathies that are frequently due to respiratory chain assembly and quality control malfunction. The aim of our analyses is to provide insight as to how translation can be coupled to the assembly of a membrane protein complex comprised of subunits of dual genetic origin and to decipher mitochondrial translational regulation coupling to the influx of imported nuclear encoded subunits." Champ scientifique sciences naturellessciences biologiquesbiochimiebiomoléculeprotéinessciences médicales et de la santémédecine fondamentalepathologie Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2013-ADG Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Coordinateur UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Adresse Robert-koch-strasse 40 37075 Goettingen Allemagne Voir sur la carte Région Niedersachsen Braunschweig Göttingen Type d’activité Higher or Secondary Education Establishments Chercheur principal Peter Rehling (Prof.) Contact administratif Christiane Hennecke (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Contribution de l’UE Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Allemagne Contribution de l’UE € 2 283 817,00 Adresse Robert-koch-strasse 40 37075 Goettingen Voir sur la carte Région Niedersachsen Braunschweig Göttingen Type d’activité Higher or Secondary Education Establishments Chercheur principal Peter Rehling (Prof.) Contact administratif Christiane Hennecke (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Autres sources de financement Aucune donnée
