ERC Advanced Grant: MITOPORE

Investigator: Ana J. García-Sáez
Project Period: 2025–2030

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 in frame of a three step process.
Ultimately, understanding the structure/function of MIM pores holds promise to guide the development of modulators against inflammatory diseases.

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