Parkinson’s disease (PD) is one of the most common disorders that affect the growing aging population and is a leading cause of disability. Approximately 60,000 Americans are diagnosed with PD each year, and an estimated 1 million in the US and 7-10 million people worldwide are living with PD. A special type of nerve cells in the brain that produces dopamine is the first to die in PD patients. These cells are highly energetic and require a large amount of energy to support their activities. This energy demand exhausts the power plants of the cell, mitochondria, which emit toxic factors to eventually kill these nerve cells. Therefore, therapeutic approaches that can protect neurons from these toxic factors and eliminate dysfunctional mitochondria hold promise to become the first disease-modifying therapies for PD. However, a roadblock to finding these exciting therapies is that we still do not understand which protein factors control these mitochondrial events. In this proposal, we will examine the role of every single gene in the cell in this process using a cutting-edge technology, CRISPR, to define this mitochondrial network. Our work will help us understand how these nerve cells die in PD and how we can reverse the cell death to treat the disease.