Project description
Studying the mechanisms of import and insertion of the proteins into mitochondrial membrane
Mitochondria are cell energy factories involved in aging and cell death. Their functions require many different proteins synthesized outside the organelle to be delivered and inserted into the right compartment. Funded by the Marie Skłodowska-Curie Actions programme, the MitoMemInsert project will focus on the mechanisms of α-helical membrane protein insertion into the mitochondrial outer membrane and on the structure of the insertase. The study will employ cryo-electron microscopy combined with magic-angle-spinning nuclear magnetic resonance spectroscopy to determine the atomic-resolution structure of mitochondrial import protein (MIM) in yeast. The results will uncover how the MIM complexes engage polypeptides to form precursor proteins for insertion into the membrane.
Objective
Mitochondria perform numerous key functions, from energy production to metabolic pathways, and are involved in ageing and cell death. All these functions rely on about 1000 different proteins, of which 99% are synthesized outside the organelle and have to be imported and inserted into the right compartment. These import and insertion are particularly demanding for the membrane proteins as they are inherently aggregation-prone. How α-helical membrane proteins (MPs) are inserted into the mitochondrial outer membrane (MOM) is currently poorly understood. In particular, the structure of the insertase responsible for inserting tens of these α-helical MPs into this membrane, called mitochondrial import protein (MIM) in yeast, is unknown. My MitoMemInsert project addresses this important knowledge gap, by determining the atomic-resolution structure of MIM, by using cryo-EM combined with magic-angle-spinning nuclear magnetic resonance spectroscopy to resolve MIM’s structure in a lipid-bilayer environment. This will open avenues to see how the MIM complex engages with polypeptides that shall be inserted into the membrane by MIM (so-called precursor proteins or ‘preproteins’). Such a “static” structure determination would already be a big leap for the field: it will be the first structure of a MOM insertase of α-helical MPs. As it is thought to have a novel architecture, this structure will provide new insights into MP insertion machinery in general. In addition, I will use NMR to study the dynamics of this machinery, which I believe, will add important mechanistic knowledge of how the MIM complex engages with MPs that are being inserted in the MOM. Overall, making use of my previous technical expertise, and adding new competences to my skill set, a combination of biophysical and structural approaches will allow me to resolve this important, and hitherto poorly addressed question in mitochondrial biogenesis and, more generally, biophysics.
Fields of science (EuroSciVoc)
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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 biochemistry biomolecules proteins
- natural sciences biological sciences biophysics
- natural sciences physical sciences optics spectroscopy
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2021-PF-01
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3400 Klosterneuburg
Austria
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