Description du projet
Le rôle des protéines mitochondriales dans la santé cellulaire
Bien que les mitochondries – les centrales électriques de la cellule – contiennent un génome mitochondrial distinct, la plupart des protéines mitochondriales sont codées par des gènes nucléaires. Elles sont donc synthétisées dans le cytosol sous forme de protéines précurseurs, puis importées dans les mitochondries. L’hypothèse de travail du projet MitoCyto, financé par l’UE, stipule que pendant leur séjour cytosolique, les protéines précurseurs mitochondriales peuvent affecter l’homéostasie cellulaire. Étant donné que l’accumulation aberrante de protéines cytosoliques est une caractéristique du vieillissement et de la neurodégénérescence, les chercheurs veulent comprendre les interactions des précurseurs cytosoliques mitochondriaux et la manière dont ils peuvent affecter la condition physique des cellules eucaryotes. MitoCyto apportera un aperçu fondamental de la biologie cellulaire; de plus, les résultats du projet seront également pertinents pour d’autres conditions que le vieillissement.
Objectif
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.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
ERC - Support for frontier research (ERC)Institution d’accueil
67663 Kaiserslautern
Allemagne