Parkinson’s disease is a destructive disease of our nervous system that affects our ability to control our movements and navigate our environments. The exact causes of Parkinson’s disease are unknown, but research suggests it may be commonly related to problems with mitochondria. Mitochondria are structures inside most cells that act like batteries, providing the cell with the energy that it needs.
Like batteries, mitochondria can become damaged and old. Cells have a disposal system to get rid of mitochondria that no longer work well. This process is called mitophagy, which literally means “mitochondria eating”. Defects in mitophagy can result in accumulation of bad mitochondria that may have detrimental effects on brain cells. There is a growing body of evidence that proteins involved in mitophagy, like Parkin and PINK1, may be at the heart of Parkinson’s disease.
Our current understanding is that the Parkin protein attaches “tags” (called ubiquitin) on damaged mitochondria so that such mitochondria can be recognized and removed. This process is important for maintaining the cell’s health.
Scientists in Genentech Research recently made a significant discovery about mitophagy and its potential role in Parkinson’s disease. They discovered a protein called USP30 that appears to clip off the “tags” that Parkin puts on old and damaged mitochondria. In follow up work, they found that Parkin creates these tags on specific locations, and that USP30 may preferentially remove tags at these specific locations. This suggests that a precise balance of Parkin and USP30 activity may be important for maintaining healthy mitochondria.
The team at Genentech found that reducing the activity of USP30 may enhance mitophagy in brain cells and that reducing USP30 may improve motor function and survival in pre-clinical animal models of Parkinson’s disease that have reduced levels of Parkin. These findings are exciting because they offer us a new insight into the basic biology of Parkinson’s disease.
Read more about these important findings in our Nature publication,"The Mitochondrial Deubiquitinase USP30 Opposes Parkin-Mediated Mitophagy," and our Nature Cell Biology publication, "USP30 and Parkin Homeostatically Regulate Atypical Ubiquitin Chains on Mitochondria."