Project description DEENESFRITPL The role of mitochondrial proteins in cell fitness Although mitochondria – the powerhouses of the cell – contain a separate mitochondrial genome, most mitochondrial proteins are encoded by nuclear genes. They are thus synthesised in the cytosol as precursor proteins and subsequently imported to mitochondria. The working hypothesis of the EU-funded MitoCyto project is that during their cytosolic residence, mitochondrial precursor proteins may affect cellular homeostasis. Considering that aberrant accumulation of cytosolic proteins is a hallmark of ageing and neurodegeneration, researchers aim to elucidate the interactions of mitochondrial cytosolic precursors and how they may affect eukaryotic cell fitness. MitoCyto will offer fundamental insight into cell biology; moreover, project results will also have relevance for conditions other than ageing. Show the project objective Hide the project objective Objective Mitochondria are made of 800 to 1500 proteins which represent up to 30% of the cellular mass. Owing to their post-translational mode of import, mitochondrial precursor proteins explore the cytosol before they are imported into mitochondria. These reactions are of utmost importance for cellular functionality since cytosolic precursors pose a major threat of cellular proteostasis and are major drivers in aging and for the pathogenesis of neurodegenerative diseases. Still, the biology of cytosolic precursors is largely elusive.In vitro import assays governed the experimentation platform of the mitochondrial community which enabled exquisite breakthroughs in understanding translocation, but are unsuited to elucidate cytosolic reactions. MitoCyto aims to break out of these experimental walls to elucidate the biology of cytosolic precursors with an interdisciplinary research team that leaves the comfort zone of biochemistry to utilize genetic and cell biology approaches but also develops novel cutting-edge techniques from high throughput approaches, through microfluidics-assisted microscopy to synthetic biology. From this innovative combination, detailed mechanistic insights into three so far largely elusive aspects of cell biology will be possible for the first time: (1) What are the cytosolic interactors of mitochondrial precursor proteins? (2) What are the direct and indirect physiological consequences of cytosolic precursor accumulation? (3) How does the re-routing of mitochondrial proteins to the nucleus control growth and fitness of eukaryotic cells?We are convinced that MitoCyto will break grounds to a comprehensive understanding of how eukaryotic cells maintain a healthy proteome over a lifetime despite fluctuating metabolic conditions. While these goals are conceptually deeply rooted in a comprehensive understanding of basic biological questions, they are of immediate relevance for cancer cell metabolism, neurodegeneration and aging. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencescell biologycell metabolismmedical and health sciencesclinical medicineoncology Keywords Mitochondria Proteostasis Aging 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 ERC - Support for frontier research (ERC) Host institution RHEINLAND-PFALZISCHE TECHNISCHE UNIVERSITAT Net EU contribution € 2 334 450,00 Address GOTTLIEB DAIMLER STRASSE 67663 Kaiserslautern Germany See on map Region Rheinland-Pfalz Rheinhessen-Pfalz Kaiserslautern, Kreisfreie Stadt 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 Total cost € 2 334 450,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all RHEINLAND-PFALZISCHE TECHNISCHE UNIVERSITAT Germany Net EU contribution € 2 334 450,00 Address GOTTLIEB DAIMLER STRASSE 67663 Kaiserslautern See on map Region Rheinland-Pfalz Rheinhessen-Pfalz Kaiserslautern, Kreisfreie Stadt 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 Total cost € 2 334 450,00
