Research project: Investigating mitochondrial-derived vesicles and their relationship to Parkinson's disease pathology

Our group has recently identified the endosomal adaptor and innate immune regulator Tollip as an essential coordinator of a Parkin-dependent mitochondrial derived vesicle (MDV) pathway. The MDV pathway is a repair mechanism that traffics damaged mitochondrial cargo to the lysosome, to preserve the integrity of the mitochondrial network and to limit cell death as a result of oxidative stress. This projects aims to elucidate the functional mechanisms associated with a Tollip-Parkin interaction and in particular how this complex regulates the transport of MDVs to the lysosome. In addition, this project will evaluate these mitochondrial quality control mechanisms in a model that more closely resembles Parkinson’s. This will entail use of neurons harvested from Thy1-SNCA mice, which overexpress alpha-synuclein, and use of alternative synuclein models developed in established cell lines. These experiments will give insight into how mitochondrial quality control is impaired following Synuclein-induced stress. Our overall objective is to determine how a Tollip-Parkin association regulates mitochondrial quality control and whether this complex is relevant in a model more closely related to disease.

Principle Investigator: David Tumbarello

Co-supervisor: Roxana Carare

PhD Student: Naomi Thorne

Funding provider:

The Gerald Kerkut Charitable Trust and University of Southampton

Funding dates: 28/09/2020 – 28/03/2024