Descrizione del progetto
Il ruolo delle proteine mitocondriali nell’idoneità delle cellule
Sebbene i mitocondri, le fucine delle cellule, contengano un genoma mitocondriale distinto, la maggior parte delle proteine mitocondriali sono codificate dai geni nucleari. Esse vengono quindi sintetizzate nel citosol come precursori delle proteine e successivamente importate nei mitocondri. L’ipotesi di lavoro del progetto MitoCyto, finanziato dall’UE, è che durante la loro permanenza nel citosol i precursori delle proteine mitocondriali possano influire sull’omeostasi cellulare. Considerando che l’accumulo anomalo di proteine citosoliche è una caratteristica dell’invecchiamento e della neurodegenerazione, i ricercatori coinvolti nel progetto intendono chiarire le interazioni dei precursori citosolici dei mitocondri e come essi possano influire sull’idoneità delle cellule eucariote. MitoCyto fornirà informazioni fondamentali sulla biologia cellulare; inoltre, i risultati del progetto saranno rilevanti anche per condizioni diverse dall’invecchiamento.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
ERC - Support for frontier research (ERC)Istituzione ospitante
67663 Kaiserslautern
Germania