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Mitochondrial nanoscale morpho-functional remodeling in MechanoMetabolism: sense force, change shape, modulate energy.

Project description

Mechanical forces and mitochondrial energy production

Mitochondria serve as the cell’s powerhouse, generating energy in the form of adenosine triphosphate (ATP) in their folded inner membrane. Mitochondria change shape depending on cellular needs, but it is still unclear how mechanical forces acting on cells affect mitochondrial function. With the support of the Marie Skłodowska-Curie Actions programme, the Mito-MechaMet project aims to investigate how mechanical forces influence the shape of mitochondria and their ability to produce energy. Using advanced imaging, mechanobiology assays and metabolic profiling, researchers will reveal how mitochondria sense and respond to their physical environment. Project findings will help explain how cells adapt their metabolism to different mechanical conditions and will provide new insights for diseases such as cancer.

Objective

Mitochondria are double-membrane organelles that sustain the bioenergetic metabolism of cells by producing ATP at the level of the cristae, convoluted folds of the inner membrane. ATP production efficiency and mitochondrial morphology, including cristae architecture, are tightly linked. Consequently, by being coupled to mitochondrial function, the reshaping of mitochondria across spatial scales regulates the cellular bioenergetic and metabolic states. Mechanical stimuli have recently been shown to modulate cellular metabolism, thus impacting physiological (e.g. cell migration, proliferation, death) and pathological (e.g. cancer progression) processes. Mechanical forces are able to reshape the global morphology of mitochondria. However, cristae remodelling upon mechanical stimuli has not yet been unravelled, and it remains unknown whether mitochondria are the key regulators of bioenergetic mechanometabolism. In Mito-MechaMet project I aim to unveil how force-induced changes in mitochondrial cristae architecture (Aim1) modulate cellular bioenergetic metabolism (Aim2) via nanoscale reorganization of proteins regulating mitochondrial shape (Aim3). These ambitious objectives will be achieved by bringing together my experience and skills on mitochondria imaging, the expertise of the host laboratory (G Giannone lab, CNRS, Bordeaux) on mechanobiology and super-resolution, and the know-how of collaborators regarding mitochondrial metabolism (BioDynaMit lab, CNRS, Bordeaux). Mito-MechaMet results will impact several fields ranging from biophysics and biomechanics to cellular biology, especially cancer biology, where mechanical cues in the tumor microenvironment critically regulate mitochondria dynamics and cancer progression. Altogether, the Mito-MechaMet project represents a uniquely tailored opportunity for me to master the necessary skills, experience and independence to pursue my long-term aspiration of leading an independent lab investigating mitochondrial biomechanics.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 211 754,88
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Ile-de-France Ile-de-France Paris
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Research Organisations
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