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PMID: 22078885 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility.

Cell ·Vol. 147 ·No. 4 ·2011-11-11 ·Pages 893-906

Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL

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.

MeSH Terms
Animals Drosophila Proteins/chemistry,metabolism Drosophila melanogaster Humans Mice Mitochondria/metabolism Mitochondrial Membranes/metabolism Mitochondrial Proteins/chemistry,metabolism Molecular Sequence Data Parkinson Disease/metabolism Phosphorylation Protein Kinases/metabolism Rats Ubiquitin-Protein Ligases/metabolism rho GTP-Binding Proteins/chemistry,metabolism
Chemicals
Drosophila Proteins Mitochondrial Proteins Ubiquitin-Protein Ligases parkin protein Protein Kinases PTEN-induced putative kinase Miro protein, Drosophila RHOT1 protein, human RHOT2 protein, human rho GTP-Binding Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wang Xinnan
F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA.
Winter Dominic
Ashrafi Ghazaleh
Schlehe Julia
Wong Yao Liang
Selkoe Dennis
Rice Sarah
Steen Judith
LaVoie Matthew J
Schwarz Thomas L
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2011.10.018
Published
2011-11-11
Pages
893-906
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3261796
Subset
IM
Grants
NIA NIH HHS · R01 AG012749 · United States
NINDS NIH HHS · R01 NS065013-03 · United States
NINDS NIH HHS · NS065013 · United States
NIGMS NIH HHS · GM069808 · United States
NIGMS NIH HHS · R01 GM069808-07 · United States
NINDS NIH HHS · R00 NS067066 · United States
NINDS NIH HHS · R01 NS065013-02 · United States
NINDS NIH HHS · R01 NS065013 · United States
NINDS NIH HHS · K99 NS067066 · United States
NIGMS NIH HHS · R01 GM069808-06 · United States
NINDS NIH HHS · K99 NS067066-01 · United States
NINDS NIH HHS · K99NS067066 · United States
NICHD NIH HHS · P30 HD018655 · United States
NIGMS NIH HHS · R01 GM069808-08 · United States
NINDS NIH HHS · K99 NS067066-02 · United States
NICHD NIH HHS · P30HD18655 · United States
NIGMS NIH HHS · R01 GM069808 · United States
Corrections
CommentIn
PMID: 22078873
CommentIn
PMID: 22146745
CommentIn
PMID: 22512003
External Links
PubMed source DOI: 10.1016/j.cell.2011.10.018 PMC Full Text View journal details
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