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How do cells eat and degrade their damaged mitochondria through mitophagy?

Project type

  • PhD
  • Honours

Project details

Cells maintain a healthy pool of mitochondria by degrading those that are damaged. This occurs through a cellular self-eating process termed mitophagy. Defects in mitophagy have been linked to human diseases, ranging from neurodegeneration (e.g. Parkinson’s disease), to cardiovascular disease.

This project will focus on understanding the mechanistic basis behind how mitophagy factors, including ubiquitin ligases, kinases, and membrane remodelling factors, contribute to mitophagy. Are they required for the formation of cellular garbage bags (termed autophagosomes) that deliver damaged mitochondria to lysosomes? Or are they required for the recognition of damaged mitochondria, so that cells can know which mitochondria to degrade? This project will explore these questions while providing experience with a variety of biochemical and cell biological techniques, including confocal microscopy, CRISPR/Cas9 gene editing, cell culture, western blotting, retrovirus transduction, molecular biology and mass spectrometry. These techniques enable students to gain experience in a range of scientific approaches and establish a strong scientific foundation to build on. This work is ideally suited for someone with a third year undergraduate background in biochemistry.

About our research group

The Lazarou lab is focused on understanding pathways that keep our mitochondria fit and healthy. This is important because failure to maintain mitochondrial health results in a range of human diseases including neurodegeneration.

Our lab has a particular interest in Parkinson’s disease, the world’s second most common neurodegenerative disorder, which affects 1-2% of people.

The pathways we explore include the removal of damaged mitochondria through mitophagy, or repair of damaged mitochondria through the mitochondrial unfolded protein response (UPRmt). Placed within the Parkinson’s Disease Research Centre at WEHI, our lab investigates the molecular mechanisms and cell biology of mitophagy pathways driven by PINK1 and Parkin, or mitochondrial receptors, including BNIP3 and NIX. Our goal is to translate our discoveries into therapies that promote mitochondrial health to help overcome disease, from Parkinson’s disease and beyond.

Education pathways