In recent years, it has become clear that even in clinically distinct neurodegenerative conditions, there are common underlying themes in how the neurons become sick and die. One such theme is a breakdown in the maintenance of mitochondria, which plays a central role in Parkinson’s disease and in other neurodegenerative conditions.
Mitochondria are the ‘energy powerhouses’ of cells. Their function is vital in long-lived neurons, where mitochondria must be maintained for an entire lifetime, and where a great deal of energy is required for them to function and survive.
The selective autophagy of damaged mitochondria (mitophagy) is critical for cell survival as it maintains optimal cellular energy production whilst avoiding the toxic accumulation of damaged mitochondria. Important information about the control of mitophagy has come from the study of the genes associated with autosomal recessive Parkinson’s disease. Of particular interest, PINK1 (mitochondrial kinase) and Parkin (E3-ubiquitin ligase) have been found to play crucial roles in mitophagy.

Against this background, our lab focuses on the following themes:
- Identifying the major molecular players in PINK1-induced mitophagy.
- Unravelling the upstream pathways that regulate the mitophagy process.
- Assessing mitophagy and other mitochondrial dysfunctions in iPSC-derived neurons from patients with Parkinson’s disease, and with other neurodegenerative diseases (E.g Alzheimer’s disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, mitochondrial DNA disease etc).

Our ultimate goal is to identify compounds that are able to modulate mitophagy and rescue mitochondrial pathophysiology and neuronal death.