Parkin mitochondria in the autophagosome

Abstract

Narendra et al. (see p. 795 of this issue) have made an exciting new discovery that links the fields of mitochondrial quality control and the genetics of Parkinson's disease (PD). Through an elegant series of high-resolution imaging experiments, they are the first to provide evidence that the PARK2 gene product Parkin is selectively recruited to damaged or uncoupled mitochondria. This recruitment leads to the clearance of the organelles through the autophagosome, demonstrating a primary function for Parkin in the regulation of mitochondrial turnover. This work significantly increases our understanding of PD and provides a new framework for the development of therapeutic interventions.

Figure 1.

Parkin recruitment leads to selective mitophagy. Cytosolic parkin is selectively recruited to uncoupled or dysfunctional mitochondria. The outer membrane protein kinase Pink1 functions upstream of Parkin and may play a role in sensing mitochondrial damage and Parkin recruitment. The ubiquitination activity of Parkin was not directly examined in this study, but it will be important to determine whether it mono- or poly-ubiquinates its substrates. The recognition of Parkin-associated mitochondrial fragments by LC3-positive autophagosome requires Atg5. Fusion with lysosomes leads to the total degradation and clearance of the damaged mitochondria. p, phosphorylation; ub, ubiquitin.