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PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility |
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| Authors: | Wang Xinnan Winter Dominic Ashrafi Ghazaleh Schlehe Julia Wong Yao Liang Selkoe Dennis Rice Sarah Steen Judith LaVoie Matthew J Schwarz Thomas L |
| Institution: | 1 F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA 2 Department of Pathology, Children's Hospital Boston, Boston, MA 02115, USA 3 Department of Neurobiology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA 4 Department of Molecular Cellular Biology, Harvard University, Cambridge, MA 02138, USA 5 Center for Neurological Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 6 Department of Cell and Molecular Biology, Northwestern University, Evanston, IL 60208, USA |
| 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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