Grant: Project Grant - PA: Nutrition, Metabolism and Diabetes

Animals like mice and humans are composed of many cells that are in turn organized into tissues or organs. For these tissues to function as a coherent unit and maintain the health of the animal, they must communicate with one another to ensure a coordinated response to a given situation (e.g. hunger, drought etc...). There is now an abundance of evidence that tissues relay signals to each other by releasing molecules into the bloodstream. The research community therefore is interested in identifying these molecules and understanding how and when they are produced and released into the circulation, the means by which other cells in the body detect them, and how these lines of communication are compromised in disease states. Recently, it has become clear that small compartments within the cell called mitochondria play a prominent role in mediating communication between some (and perhaps all) tissue types. Consistent with this idea, our lab has discovered that the liver secretes a protein into the bloodstream when its mitochondria are stressed that then exerts significant effects on the viability of immune cells. We therefore propose to characterize this novel signaling pathway because it will greatly advance our understanding of physiology, and may lead to the identification of therapeutic targets that can be leveraged to treat mitochondrial disease patients to improve their quality of life.