Abstract

Mitochondrial dysfunction has long been suspected to play a role in the pathogenesis of Parkinson’s disease. This hypothesis has received strong support in recent years, with the discovery of gene responsible for familial Parkinson’s disease playing roles in mitochondrial maintenance. The products of the PINK1 and PARK2 (Parkin) genes cooperate in sensing mitochondrial dysfunction and linking it to the activation of protective mitochondrial quality control programs, including mitophagy. Despite the remarkable advances in our understanding of the molecular mechanisms by which PINK1 and Parkin promote mitophagy, little is known about how their dysfunction leads to neuronal degeneration. I will present recent efforts from our laboratory to characterize mechanisms by which PINK1 and Parkin preserve the quality of mitochondria and understand how dysfunction of this multifunctional pathway leads to neuronal degeneration in Parkinson’s disease.