Mitochondrial quality control turns out to be the principal suspect in parkin and PINK1-related autosomal recessive Parkinson's disease

Mitochondrial dysfunction has long been suspected to play a key role in neurodegeneration in Parkinson's disease. PINK1 and Parkin, the products of two genes responsible for autosomal recessive Parkinsonian syndromes with early onset, act as a quality control system on the outer mitochondrial membrane to preserve mitochondrial integrity. While doing so, they interact with multiple molecular actors in processes regulating mitochondrial biology and cell survival. The physiological conditions that mobilize these processes in neurons, and the mechanisms underlying their integration and spatiotemporal coordination, remain to be elucidated. Understanding how dysfunction of these house-keeping pathways leads to the preferential degeneration of a specific neuronal population in Parkinson's disease is a major challenge for future research.

► Blockade of protein import stabilizes PINK1 on mitochondria and triggers mitophagy. ► Proteasome degradation of OMM proteins initiates mitochondrial clearance. ► The PINK1/Parkin pathway promotes mitochondrial clearance in neurons. ► Multiple functions of PINK1 and Parkin converge on mitochondrial quality control.