Seminaire SOLEIL - Montserrat SOLER-LOPEZ - 14 sept à 14h00 - Amphi SOLEIL

Mitochondrial Bioenergetics in Alzheimer’s Disease : Insights from the European Synchrotron 

Montserrat SOLER-LOPEZ 
Macromolecular X-ray Crystallography, Imaging and Scattering Group, European Synchrotron RadiationFacility (ESRF), Grenoble, France

Lundi 14 septembre 2026 – 14h00 - Amphithéâtre SOLEIL

Alzheimer's disease (AD) is increasingly linked to defects in mitochondrial bioenergetics. At the ESRF, we investigate  the  mechanisms  underlying  this  dysfunction,  focusing  on  respiratory  complex  I  and  its assembly  factors.  Using  an  integrative  approach  combining  macromolecular crystallography, cryo- electron microscopy, X-ray imaging, and spectroscopy, we reveal novel regulatory mechanisms of energy metabolism, including phosphorylation-dependent modulation at the interface of respiration and fatty acid oxidation. We further demonstrate that AD-related amyloid oligomers disrupt these processes in neuronal mitochondria, contributing to oxidative stress and impaired  bioenergetics. These findings highlight how interdisciplinary methodologies advance our understanding of neurodegeneration, offering new perspectives for targeting mitochondrial dysfunction in AD.

[1] Giachin et al. Dynamics of Human Mitochondrial Complex I Assembly: Implications for  Neurodegenerative Diseases. Front. Mol. Biosci. 2016, 3:43 
[2] McGregor & Soler-Lopez. Structural basis of bioenergetic protein complexes in Alzheimer's disease pathogenesis. Cur Opin Struct Biol. 2023, 80:102573 
[3] Giachin et al. Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory  Role for Deflavination. Angew. Chem. Int. Ed. 2021, 60(9):4689 
[4] McGregor et al. The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox  pathway coordination. Nat Commun. 2023, 14(1):8248  

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