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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2011 Nov 15

PMID 22078885

Citations 639

Authors

Xinnan Wang

Dominic Winter

Ghazaleh Ashrafi

Julia Schlehe

Yao Liang Wong

Dennis Selkoe

Sarah Rice

Judith Steen

Matthew J LaVoie

Thomas L Schwarz

Affiliations

Soon will be listed here.

Abstract

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.

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