How a very “sociable” protein can hold clues about Alzheimer’s origins - M. Soler Lopez -

QUICK INFORMATION
Type
Webinar
Start Date
05-02-2021 14:00
End Date
05-02-2021 15:00
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Coordinator contact(s)
Anne-Françoise Maydew

Scientific contact(s)
Patrick Bruno


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INVITATION

#ESRFscience Live Online Seminars
 

"How a very 'sociable' protein can hold clues about Alzheimer's origin"

Friday, February 5th at 14:00

Presented by Monterrat Soler Lopez, ESRF scientist

 

ABSTRACT

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 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 [3]. 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 [4], our findings might help unveil the causal link between mitochondrial dysfunction and amyloid pathology in the early stages of AD.
 

Please click here to watch the webinar in replay:
https://www.youtube.com/watch?v=fQ9hrJeklms&t=1883s


Funding: The organisation of this online seminar series is supported by STREAMLINE, a European project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870313.

 

References:

[1] Soler-Lopez et al. (2011) Interactome mapping suggests new mechanistic details underlying Alzheimer's disease. Genome Res. 21(3):364-76.

[2] Soler-Lopez et al. (2012) Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction. Hypothetical role of the adapter protein ECSIT in familial and sporadic Alzheimer's disease pathogenesis. Bioessays 34(7):532-41.

[3] Giachin et al. (2021) Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination. Angew. Chem. Int. Ed. 60: 2-11.

[4] Giachin et al. (2016) Dynamics of Human Mitochondrial Complex I Assembly: Implications for Neurodegenerative Diseases. Front. Mol. Biosci. 3:43.