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Mitochondrial Precursor Proteins in the Cytosol as Major Determinants of Cellular Health

Project description

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.

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.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-ADG

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Host institution

RHEINLAND-PFALZISCHE TECHNISCHE UNIVERSITAT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 334 450,00
Address
GOTTLIEB DAIMLER STRASSE
67663 Kaiserslautern
Germany

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Region
Rheinland-Pfalz Rheinhessen-Pfalz Kaiserslautern, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 334 450,00

Beneficiaries (1)

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