Project description
A closer look at mitochondrial pores
Inflammation is the body’s first line of defence against damage. However, when it gets out of hand, it can lead to chronic disease. Mitochondria, which are the energy centres of cells, play an important role. Due to their bacterial origins, the contents leaking from mitochondria can activate strong immune responses. Even though it is known how pores form in the outer mitochondrial membrane, how they form in the inner membrane remains unclear. The ERC-funded MITOPORE project uses advanced imaging and molecular profiling to identify the pores in the inner membrane and to understand how they trigger inflammation. The discoveries could provide insights that might lead to treatments for inflammatory disorders.
Objective
Mitochondria are double-membrane organelles involved in key biological processes such as metabolism, calcium homeostasis and cell death. A major role of mitochondria in inflammation, a mechanism of innate immunity against tissue damage, has been recently recognized. Due to their proteobacterial origin, certain mitochondrial matrix contents can act as potent immune agonists when exposed to the cytosol. Hence, knowing the dynamics and molecular architecture of the mitochondrial pores mediating the release of these mitochondrial contents is crucial for understanding the role of mitochondria in inflammation.
While in apoptosis BAX and BAK proteins form pores at the mitochondrial outer membrane (MOM), the components and mechanisms that regulate the permeabilization of the mitochondrial inner membrane (MIM) remain unknown. MITOPORE aims to unravel the identity, dynamic architecture and regulation of the pores that permeabilize the MIM and to understand how they control mitochondria-driven inflammation. We will reach this goal by building on our expertise in membrane biology and advanced imaging to:
1) Identify the mediators and regulators as well as the physical forces controlling MIM pores with complexome profiling and image-based biophysical analysis.
2) Define their contribution to anti-mitochondria immunogenicity through activation of intracellular immune receptors and communication with the tissue microenvironment in cellular and in vivo models.
3) Determine the assembly dynamics and molecular structure of MIM pores and their regulators by combining single particle and super-resolution imaging and advanced electron microscopies.
MITOPORE is expected to provide textbook knowledge about the mitochondrial contribution to inflammation. The established workflows will open new avenues for membrane and organelle biology research. Ultimately, understanding the structure/function of MIM pores holds promise to guide the development of modulators against inflammatory 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 chemical sciences inorganic chemistry alkaline earth metals
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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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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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.
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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-ADG
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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.
80539 MUNCHEN
Germany
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