Objective "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." Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathology 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) Topic(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2013-ADG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Address Robert-koch-strasse 40 37075 Goettingen Germany See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Principal investigator Peter Rehling (Prof.) Administrative Contact Christiane Hennecke (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 2 283 817,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Germany EU contribution € 2 283 817,00 Address Robert-koch-strasse 40 37075 Goettingen See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Principal investigator Peter Rehling (Prof.) Administrative Contact Christiane Hennecke (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window
