PINK1 and Parkin target miro for phosphorylation and degradation to arrest mitochondrial motility

Xinnan Wang, Dominic Winter, Ghazaleh Ashrafi, Julia Schlehe, Yao Liang Wong, Dennis Selkoe, Sarah Rice, Judith Steen, Matthew J. Lavoie, Thomas L. Schwarz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

683 Scopus citations

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. PaperFlick:

Original languageEnglish (US)
Pages (from-to)893-906
Number of pages14
JournalCell
Volume147
Issue number4
DOIs
StatePublished - Nov 11 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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