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Content archived on 2024-05-27

Regulation of mitochondria-endoplasmic reticulum tethering by Parkin: implication for Parkinson’s disease

Objective

Parkin, an E3 ubiquitin ligase and a Parkinsons's disease related gene, translocates to impaired mitochondria upon mitochondria intoxication and drives their elimination via autophagy, a process known as mitophagy. Mitochondrial pro-fusion protein Mitofusin (Mfn) was found to be a target for Parkin mediated ubiquitination. In absence of Parkin, Mfn fails to be ubiquitinated, thus accumulates in the mitochondria, leading to increased mitochondria fusion. The host laboratory discovered that Mfn2 has an additional role in tethering mitochondria to endoplasmic reticulum (ER), a structural feature essential for Ca2+ transfer between the organelles and Ca2+ dependent cell death. This project hypothesizes that Parkin dependent ubiquitination of Mfn is crucial in regulating mitochondria-ER tethering and neuronal survival. We therefore aim to (i) address whether impairment of Parkin-dependent Mfn ubiquitination affects mitochondria-ER tethering and death by Ca2+-dependent stimuli; (ii) identify a potential Deubiquitinase (DUB) enzyme opposing Parkin activity in the regulation of Mfn ubiquitination; iii) identify novel interactors of the PINK1/Parkin pathway, regulating Parkin translocation to mitochondria and therefore Mfn steady-state levels. This project will therefore clarify if ER-mitochondria tethering participates in the neurodegenerative pathways controlled by Parkin

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2010-IEF
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITE DE GENEVE
EU contribution
€ 178 101,60
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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