Understanding mtDNA escape during cell death and disease

Mitochondria more than just “the powerhouse of the cell”. They are fascinating, highly dynamic organelles that carry out an array of cellular functions; all the while sitting at the crossroads of cellular fate – mitochondria can release the power for life, and just as easily unleash the machineries of death. Due to their evolutionary past-life as an a-proteobacteria, mitochondria also harbor molecules that are highly immunogenic if released from within. Case in point, mitochondrial harbor their own genome – mtDNA – which when released outside the mitochondria, triggers potent immune responses from the host. Mislocalised mtDNA has been implicated in a wide variety of pathologies – including Rheumatoid Arthritis, Lupus, Parkinson’s Disease, Sepsis, Stroke, Cancer, HIV, Dengue infection, and even Covid-19 infection – yet so little is known about how it is released, what the immune consequences are, and how this contributes to disease. This project blends biochemistry and cell biology with state-of-the-art microscopy techniques (both light microscopy and electron microscopy) to understand the mechanism and consequences of mtDNA release and mitochondrial behaviour in cellular and animal models of disease.