Objective The mitochondrial network produces the bulk part of the energy mammalian cells need through the oxidative phosphorylation process. The importance of mitochondria is underscored by the fact that deficient oxidative phosphorylation causes a wide number of genetic diseases. It is also heavily implicated in age-associated disease and ageing. Expression of mammalian mtDNA is of key importance for maintaining mitochondrial oxidative phosphorylation but studies of the poorly understood regulation of mammalian mitochondrial gene expression offer substantial experimental challenges. In the late 1990s, we felt that the challenges associated with understanding mammalian mtDNA gene expression could only be tackled by a broad interdisciplinary scientific approach. We therefore started collaboration between the Larsson (expertise in mouse genetics, in vivo physiology and cell biology) and Gustafsson laboratories (expertise in biochemistry, recombinant in vitro systems, structural biology) that has been ongoing for more than a decade. The success of this collaborative effort is documented by many joint publications in high-profile journals. Most importantly, we have together molecularly defined the basal mtDNA transcription initiation machinery and discovered a novel repressor, MTERF3, of mtDNA transcription. In this proposal, we present a series of unpublished results showing quite unexpected complexity in the regulation of mtDNA expression. An important part of our proposed work will be to establish how the different levels of regulation of mtDNA gene expression communicate to achieve a coordinated response to physiological stimuli. Fields of science natural sciencesbiological sciencesbiochemistrynatural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencescell biologymedical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesmolecular biologystructural biology 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-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Address Hofgartenstrasse 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Salvatore Angilletta (Mr.) Principal investigator Nils-Göran Larsson (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany EU contribution € 2 000 000,00 Address Hofgartenstrasse 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Salvatore Angilletta (Mr.) Principal investigator Nils-Göran Larsson (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data GOETEBORGS UNIVERSITET Sweden EU contribution € 1 110 000,00 Address Vasaparken 405 30 Goeteborg See on map Region Södra Sverige Västsverige Västra Götalands län Activity type Higher or Secondary Education Establishments Administrative Contact Ludde Edgren (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
