Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by the formation of amyloid-β (Aβ) plaques in the brain and whose causality remains unclear. Today, a worldwide effort is underway to identify the factors that trigger AD. Mitochondria, which coordinate central functions in the cell and have a crucial role in energy metabolism, degrade with age and are heavily perturbed in AD patients, thus becoming prime suspects in the onset of AD.
Our research focuses on the mitochondrial energy pathways that couple redox reactions to ATP production and how they might affect, or be affected, by Aβ toxicity. In previous work, we identified the multitask protein ECSIT (Evolutionarily Conserved Signaling Intermediate in Toll pathway) as a potential player in amyloid pathology [1,2] in addition to its role as an assembly factor of the mitochondrial respiratory Complex I, a 1MDa protein complex.
While exploring the molecular basis for ECSIT protein recognition in CI assembly, using SAXS and cryo-electron microscopy coupled with biochemical and biophysical experiments, we have discovered a unique mechanism of enzyme regulation with implications for the coordination of metabolic mitochondrial pathways that are required to ensure efficient energy production . Furthermore, we have also found that ECSIT is very sensitive to the presence of amyloids in mitochondria. Given the involvement of Complex I in neurodegenerative processes , our findings might help unveil the causal link between mitochondrial dysfunction and amyloid pathology in the early stages of AD.
More information can be found on our webpages: https://www.esrf.fr/home/events/webinars/content/area-events/past-online-seminars/how-a-very-sociable-protein-can-hold-clues-about-alzheimers-origins—m-soler-lopez–.html