Project description
Molecular basis of correlation between mitochondrial DNA copy number and cell volume
Mitochondria – eukaryotic cells’ energy factories – have their own DNA, producing proteins essential to mitochondrial function. Mitochondrial number increases when a cell’s energy needs increase. Mitochondrial DNA (mtDNA) copy number, a measure of mtDNA amount, is associated with energy production, but how it is maintained during cell proliferation and how it affects cell function are not clear. The ERC-funded MITOSIZE project aims to investigate the molecular basis of an observed correlation between mtDNA copy number and cell volume. Using molecular biology, live cell imaging and computational methods, it will see if nuclear-encoded mtDNA maintenance factors produced in proportion to cell volume limit mtDNA replication and stability.
Objective
Mitochondrial DNA (mtDNA) constitutes a substantial proportion of DNA in eukaryotes, and its regulation is critical not only for mitochondrial function but also for cell survival. However, it is still unclear how mtDNA copy number is maintained during cell proliferation and how mtDNA copy number impacts on cell function. Recently, my group showed that in budding yeast, mtDNA copy number is tightly linked to cell volume to maintain constant concentrations, providing an elegant and potentially conserved strategy for mtDNA homeostasis. But how is mtDNA coupled to cell volume? Based on my group’s work, we proposed that nuclear-encoded mtDNA maintenance factors produced in proportion to cell volume limit mtDNA replication and stability. This provides a conceptual mechanism for how cells link mtDNA copy number to total cellular protein content, and opens the door to a quantitative and molecular understanding of mtDNA homeostasis.
With MITOSIZE, I will reveal the molecular basis of this ‘limiting machinery’ mechanism. To test whether the mechanism is conserved across species and to chloroplast DNA, I will use two evolutionary distant eukaryotes: S. cerevisiae, whose size I can control genetically, and C. reinhardtii, whose size I can control with light. I will use an interdisciplinary approach combining molecular biology, quantitative live-cell imaging, and modelling to develop a quantitative understanding based on measurements of mtDNA replication and degradation. I will then unravel the contribution of the ‘limiting machinery’ regulation to the dynamic adaptation of mtDNA to changing environments. Moreover, by breaking the coupling of mtDNA copy number to cell volume, I will dissect how cell volume and mtDNA copy number determine cell function and aging. By identifying the molecular regulation underlying organellar DNA homeostasis, I will address a fundamental question in cell biology and open the door to new intervention strategies for mtDNA misregulation in diseases.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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(opens in new window) ERC-2024-COG
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85764 Neuherberg
Germany
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