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The University of Southampton
Biological Sciences

Research project: Investigating the mechanisms of Parkin-mediated mitophagy

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Project type: 
Grant

Determining how cells maintain homeostasis under times of stress is vital to understanding a wide range of disorders, from neurodegenerative diseases to cardiomyopathies. This project aims to delineate crucial mechanisms that regulate mitochondrial homeostasis during times of stress in order to understand how cells limit their damage.

Following cellular stress and acute damage, intracellular degradation pathways are activated in order to maintain homeostasis. Once such mechanism is the autophagy pathway, which maintains balance by providing a nutrient source during starvation and limiting cellular damage by enabling an efficient mechanism for degradation of misfolded proteins and damaged organelles. Mitophagy is a selective form of autophagy specific for mitochondria, primarily facilitated by ubiquitin-tagging, sequestration of damaged mitochondria within an autophagosome, and degradation by the lysosome. One such mechanism of this process requires recruitment of the E3 ubiquitin ligase parkin (PARK2) which facilitates recognition of damaged mitochondria by the autophagic machinery, thus promoting their clearance from the cell. The primary aim of this proposal is to determine the requirements for parkin recruitment to damaged mitochondria and delineate the role as well as mechanisms of action of a particular adaptor protein complex during mitophagy. The outcomes of this project will contribute significant advances to the underlying mechanisms and crucial regulators of mitophagy, while providing valuable information on how cells maintain homeostasis and how dysfunction leads to disease.

Importantly, outcomes of this proposal will help provide key information namely - how parkin is recruited to mitochondria in response to pharmacological induced damage. These results will have significant implications in Parkinson’s, as well as other neurodegenerative and cardiovascular diseases, which have implicated mitophagy as a crucial regulator of cell homeostasis.

Funding: Wellcome Trust
Funding duration: May 2017 - May 2019

Related research groups

Biomedical Sciences
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