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

被引：1066

作者：

Wang, Xinnan ^{[1
,3
]}

Winter, Dominic ^{[2
]}

Ashrafi, Ghazaleh ^{[1
,4
]}

Schlehe, Julia ^{[5
]}

Wong, Yao Liang ^{[6
]}

Selkoe, Dennis ^{[5
]}

Rice, Sarah ^{[6
]}

Steen, Judith ^{[1
,2
]}

LaVoie, Matthew J. ^{[5
]}

Schwarz, Thomas L. ^{[1
,3
]}

机构：

[1] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[2] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA

[4] Harvard Univ, Dept Mol Cellular Biol, Cambridge, MA 02138 USA

[5] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[6] Northwestern Univ, Dept Cell & Mol Biol, Evanston, IL 60208 USA

来源：

CELL | 2011年 / 147卷 / 04期

关键词：

AXONAL-TRANSPORT; PINK1/PARKIN PATHWAY; DOPAMINERGIC-NEURONS; DEFICIENT MICE; DROSOPHILA; DISEASE; MUTATIONS; MITOPHAGY; INTERACTS; KINESIN;

D O I：

10.1016/j.cell.2011.10.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：893 / 906

页数：14

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