Parkinson’s disease is the second most common neurodegenerative disease, affecting over 10 million people worldwide. Some forms of Parkinson’s disease are characterized by an inability of cells to clean up dysfunctional mitochondria, the cells’ “powerhouses,” particularly in neural cells of the brain. Like batteries, the mitochondria provide energy for a cell to function, but also like batteries, they can leak toxins as they age. Mitophagy is the process by which cells conduct quality control, throwing away old and defective mitochondria like taking out the trash.
Now, a new study from Caltech reports that two candidate drugs to activate mitophagy do not function in their intended manner to mitigate the effects of Parkinson’s; instead, they simply damage cells.
The research is described in a paper appearing in Science Advances on August 27, titled “Putative PINK1/Parkin Activators Lower the Threshold for Mitophagy by Sensitizing Cells to Mitochondrial Stress.”. The study was led by former graduate student William Rosencrans (PhD ’25) and is a collaboration between the laboratories of Tsui-Fen Chou, research professor of biology and biological engineering, and David Chan, Harold and Violet Alvarez Professor of Biology and dean of graduate studies. Chou and Chan are both affiliated faculty members with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.