We aim to unravel the regulation of mitochondrial homeostasis in health and disease.
Mitochondrial signalling: a matter of life and death
Mitochondria do it all. They carry the genetic signature of our maternal lineage, are critical to cell viability and produce the chemical energy required for our cells and tissues to survive. Their unique morphology even reflects our bacterial past. It is now widely appreciated that mitochondria serve as essential platforms for a variety of molecular reactions witin our cells. Despite their static textbook depiction, these membrane bound organelles form a remarkably dynamic network in our cells.
It is not suprising therefore that mitochondrial damage and abbarent mitochondrial metabolism is linked to a variety of human diseases, including neurodegeneration (Parkinson's disease, ALS), ageing, immune dysfunction, certain forms of cancer and inheirited mitochondrial disorders. Consequently, our cells have evolved multiple mechanisms to cope with mitochondrial meltdown.
Mitophagy: selective delivery of damaged mitochondria to the lysosome for destruction
One way to deal with damaged mitochondria is to destroy them. Autophagy is an essential catabolic pathway that evolved to sustain cells during times of nutrient deprivation. It is widely appreciated that autophagy can be both non-selective (macroautophagy) and selective. Over the past decade, pioneering work from many laboratories has demonstrated that damaged mitochondria can be selectively eliminated, in a process known as "mitophagy". Although traditonally researched as a stress-response pathway, it is now emerging that various mitophagy pathways exist in mammals. Indeed, different cells within the same organ exhibit striking heterogenity.
Tackling a complex question in tissues: in vivo mitophagy
Understanding the regulation of mitophagy in vivo is particularly complex and could not be addressed until recently. My laboratory combines sophisticated mouse genetics and cutting edge approaches in neuroscience, microscopy and biochemistry to understand the endogenous regulation of mitophagy pathways in vivo. A major goal of our research is to both exploit and develop tools to understand mitochondrial homeostasis in health and disease.