PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility

Cells keep their energy balance and avoid oxidative stress by regulating mitochondrial movement, distribution, and clearance. We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement. PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. Removal of Miro from the mitochondrion also detaches kinesin from its surface. By preventing mitochondrial movement, the PINK1/Parkin pathway may quarantine damaged mitochondria prior to their clearance. PINK1 has been shown to act upstream of Parkin, but the mechanism corresponding to this relationship has not been known. We propose that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome. [Display omitted] [Display omitted] ► PINK1 or Parkin expression arrests the movement of neuronal mitochondria ► PINK1 and Parkin associate with the motor/adaptor Miro on depolarized mitochondria ► PINK1 phosphorylates Miro and causes it to be degraded by the proteasome ► PINK1 requires Parkin to cause Miro degradation Two proteins implicated in Parkinson's disease function to quarantine damaged mitochondria. They sever ties to the microtubule network by triggering degradation of the kinesin adaptor Miro.