Grant: Operating 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 has uncovered a totally 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. We know that some of the proteins required for these vesicles to form are mutated in patients with Parkinson's disease. Therefore we will determine whether mitochondrial vesicles play a critical role in neurons, and look for ways to enhance this process in aging cells. This work will help us understand how to maintain mitochondria, and increase human health and longevity.