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)
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 biochemistry biomolecules proteins
- natural sciences biological sciences biophysics
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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.
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
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
See all projects funded under this callCoordinator
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.
3400 KLOSTERNEUBURG
Austria
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.