Grant: Project Grant

Inside of every cell there are many mitochondria, which are membrane-bound structures that use the oxygen we breath to combust fat and sugar, which generates cellular energy in the form of ATP. During the consumption of oxygen, the mitochondria are exposed to damaging superoxide radicals, which can react with the lipid and protein machines within the mitochondria. This reaction often inactivates the proteins and enzymes, which must be removed or degraded in order for them to keep mitochondria working properly. Our lab discovered a new way for the mitochondria to eject their damaged material. We have shown that damaged material aggregates and is released from the mitochondria in a small, vesicular, membrane-bound "pod". This vesicle is transported to the "garbage can" of the cell, or lysosome, where it fuses so the material may be degraded. The current proposal aims to define the mechanisms that generate these vesicles, and discover how the cargoes are chosen that are removed and degraded through mitochondrial vesicles. We recently uncovered an itinerary of content within these vesicles which will act as a roadmap for our ongoing discovery. Since our discovery of mitochondrial vesicles, many other labs have identified critical roles for their formation in cancer, aging, neurodegenerative disease and during infection. Therefore it is critical that we identify the core mechanisms of their formation, their regulation, and ultimately, the functional importance of vesicle transport in human health and disease.