Grant: Project Grant

The cell is a highly ordered and compartmentalized place with intracellular organelles carrying protein, lipid and signals throughout the cell. In addition to these carriers, there are two important compartments in the cell that perform a host of essential biochemical reactions, mitochondria and peroxisomes. Mitochondria are primarily known as the "energy powerhouse" of the cell, recycling sugar, protein and fat into cellular energy. However, there are many other reactions that occur in mitochondria and a host of these reactions rely on a second, smaller organelle called the peroxisomes to complete the chain reaction and build, or degrade, the final product. For example, the breakdown of very long chain fatty acids occurs first in peroxisomes, and the resulting shorter chain lipids are then transferred to mitochondria to be burned as energy. Without peroxisomes this cannot occur and the very long chain fatty acids are highly toxic, causing cell death and disease. In other cases enzymes in each organelle work sequentially to build new molecules, like bile acids in liver, or unique protective lipids called plasmalogen in the brain. The extent of the relationship between mitochondria and peroxisomes is so high that they share a number of common proteins, and we have shown that there is a direct, vesicle based delivery of protein and lipid from mitochondria to peroxisomes both in steady state, and for the formation of newly born peroxisomes. This proposal aims to understand how and why this type of vesicle transport exists in health and disease. There are many devastating diseases, both rare and more common, where peroxisomes or mitochondria are dysfunctional and we are currently without any therapy to treat them. By understanding the molecular basis of the integration between these two organelles we can contribute to the strategic design of new therapies to target disease.