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Super-Resolution deciphers DRP1's Cut: Mitochondrial Fission during Apoptosis via SMLM and MINFLUX

Objective

Illnesses such as neurodegenerative diseases and cancer represent significant public health challenges due to their increasing prevalence, mortality rates, and societal impact. Mitochondrial dysfunction, specifically the dysregulation of mitochondrial fission, is implicated in these diseases.
Together with mitochondrial fusion, the mitochondrial fission process, or the division of mitochondria, is essential for maintaining cellular health. The effector protein of mitochondrial fission is the dynamin-related protein 1 (DRP1). During cell death, mitochondrial fission is elevated and DRP1 interacts with the key apoptotic proteins BAX and BAK. However, the precise role, regulation, and positioning of DRP1 in mitochondrial fission, especially with regards to BAX and BAK during apoptosis remain unclear.
The project SuperCut will unravel the molecular architecture of DRP1 as well as its motion pattern during mitochondrial fission in the context of apoptosis by using advanced super-resolution microscopy techniques. Single-molecule localization microscopy (SMLM) will enable the visualization of the spatial organization of DRP1 and its relation to apoptotic pore formed by BAX and BAK. MINFLUX tracking will provide insights into the spatial dynamics of DRP1 and its adaptors in healthy cells and their interaction with BAX and BAK in apoptotic cells. By elucidating these mechanisms, the project will open new avenues for innovative therapeutic strategies targeting dysfunctional mitochondrial fission.
The research for SuperCut will be conducted by me, Dr. Sarah Schweighofer at the Max Perutz Laboratories under the supervision of Prof. Jonas Ries, leveraging cutting-edge microscopy techniques to push the boundaries of our understanding of mitochondrial dynamics in health and disease. This deepening of my super-resolution microscopy expertise will enable me to become an independent multidisciplinary scientist with high impact in the life sciences.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

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Coordinator

UNIVERSITAT WIEN
Net EU contribution
€ 214 344,72
Address
UNIVERSITATSRING 1
1010 Wien
Austria

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Region
Ostösterreich Wien Wien
Activity type
Higher or Secondary Education Establishments
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