Project description DEENESFRITPL Mechanistic insight into mitochondrial gene expression Apart from nuclear DNA, eukaryotic cells contain mitochondrial DNA, which encodes subunits of the electron transport chain enzymes. Although this clearly indicates the importance of mitochondrial gene expression for cellular metabolism, little mechanistic insight is available on how it is achieved and regulated. Mitochondrial gene translation is already known to undergo regulation through the action of nuclear-encoded factors. Funded by the European Research Council, the MiXpress project proposes to investigate the different steps in the mitochondrial gene expression process. Emphasis will be given on the cooperation with nuclear-encoded components to understand how cells respond to energy needs. Show the project objective Hide the project objective Objective Mitochondrial gene expression is essential for cellular metabolism and energy supply since 13 core subunits of the OXPHOS system are encoded on the mitochondrial genome. Despite its importance for cellular function, mitochondrial gene expression (mitoGE) and its regulation are not understood at a mechanistic level. To this end, we demonstrated that mitochondrial translation is prone to regulation, responding to influx of nuclear-encoded proteins . However, the mechanisms that regulate gene expression in mitochondria remain unknown. A lack of suitable experimental approaches to modulate mitoGE hampers progress in our understanding. Here I propose a project that takes the next big step towards understanding the mechanisms of mitochondrial gene expression. Our recent work on an in organello system to target mitoGE in a transcript-specific manner provides the bases for the challenging project proposed here, which aims to solve long-standing questions: First, we will dissect mitochondrial transcript interactomes and their spatial orchestration to understand basic principles of RNA abundance, organization in granules, and cross communication. Second, we are now able to investigate translation in the context of the inner membrane with transcript-specific resolution and thereby identify liaising factors involved in ribosome recruitment and membrane insertion and regulation. Third, we will extend our strategy towards an in vivo transcript-specific silencing approach to define retrograde signaling pathways that integrate mitoGE into cellular contexts. The combination of functional analyses carried out in organello and in vivo will provide unprecedented insights into components and mechanism of mitoGE and reveal how two genetically independent systems cooperate to build a functional metabolic pathway able to respond to energetic requirements and challenges. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysisnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-ADG - ERC ADVANCED GRANTS Call for proposal ERC-2021-ADG See other projects for this call Funding Scheme HORIZON-AG - HORIZON Action Grant Budget-Based Coordinator UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Net EU contribution € 1 913 968,00 Address Robert-koch-strasse 40 37075 Goettingen Germany See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
