Mitochondrial cristae disorganization and neuroinflammation: a deleterious link leading to neuronal death. 2024-2026, FRM-Maladies neurodégénératives, PI Sylvie Bannwarth

Our project seeks to explore molecular mechanisms linking mitochondrial cristae loss, neuroinflammation and neurodegenerative diseases. Mitochondrial cristae architecture is critical to maintain ATP production through respiratory chain integrity. Loss of cristae is observed in various mitochondrial diseases dues to mutations in genes encoding proteins essential for cristae architecture. Patients develop neurodegenerative pathologies with energy defect and neuroinflammation.

Using various cellular and mice models, all of which showing disorganization of mitochondrial cristae due to mutations in different genes, we will (i) compare molecular mechanisms responsible for loss of cristae integrity, (ii) decipher inflammatory pathways and their neurotoxic potential and (iii) identify novel therapeutic targets for neurodegenerative diseases.