Regulation of PINK1-Parkin-mediated mitophagy

Abstract

Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.