PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy

被引：199

作者：

Kawajiri, Sumihiro ^{[1
]}

Saiki, Shinji ^{[1
]}

Sato, Shigeto ^{[1
]}

Sato, Fumiaki ^{[2
]}

Hatano, Taku ^{[1
]}

Eguchi, Hiroto ^{[1
]}

Hattori, Nobutaka ^{[1
]}

机构：

[1] Juntendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo 1138421, Japan

[2] Juntendo Univ, Sch Med, Res Inst Dis Old Age, Bunkyo Ku, Tokyo 1138421, Japan

来源：

FEBS LETTERS | 2010年 / 584卷 / 06期

关键词：

PTEN-induced putative kinase 1; Parkin; Mitophagy; Autophagy; Parkinson's disease; OXIDATIVE STRESS; MUTATIONS; DROSOPHILA-PINK1; DYSFUNCTION; PROMOTES; MUTANTS;

D O I：

10.1016/j.febslet.2010.02.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive form of Parkinson's disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions. Here, we show that PINK1 in combination with parkin results in the perinuclear mitochondrial aggregation followed by their elimination. This elimination is reduced in cells expressing PINK1 mutants with wild-type parkin. Although wild-type PINK1 localizes in aggregated mitochondria, PINK1 mutants localization remains diffuse and mitochondrial elimination is not observed. This phenomenon is not observed in autophagy-deficient cells. These results suggest that mitophagy controlled by the PINK1/parkin pathway might be associated with PD pathogenesis. Structured summary: MINT-7557195: PINK1 (uniprotkb: Q9BXM7) physically interacts (MI: 0915) with LC3 ( uniprotkb: Q9GZQ8) by anti tag coimmunoprecipitation ( MI: 0007) MINT-7557109: LC3 ( uniprotkb: Q9GZQ8) and PINK1 ( uniprotkb: Q9BXM7) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416) MINT-7557121: tom20 ( uniprotkb: Q15388) and PINK1 ( uniprotkb: Q9BXM7) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416) MINT-7557138: parkin ( uniprotkb: O60260), PINK1 ( uniprotkb: Q9BXM7) and tom20 ( uniprotkb: Q15388) colocalize ( MI: 0403) by fluorescence microscopy ( MI: 0416) MINT-7557173: LC3 ( uniprotkb: Q9GZQ8) physically interacts ( MI: 0915) with PINK1 ( uniprotkb: Q9BXM7) by anti bait coimmunoprecipitation ( MI: 0006) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：1073 / 1079

页数：7

共 20 条

[1] Expanding insights of mitochondrial dysfunction in Parkinson's disease [J].

Abou-Sleiman, PM ;

Muqit, MMK ;

Wood, NW .

NATURE REVIEWS NEUROSCIENCE, 2006, 7 (03) :207-219

[2] Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability [J].

Beilina, A ;

Van Der Brug, M ;

Ahmad, R ;

Kesavapanyt, S ;

Miller, DW ;

Petsko, GA ;

Cookson, MR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (16) :5703-5708

[3] Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin [J].

Clark, Ira E. ;

Dodson, Mark W. ;

Jiang, Changan ;

Cao, Joseph H. ;

Huh, Jun R. ;

Seol, Jae Hong ;

Yoo, Soon Ji ;

Hay, Bruce A. ;

Guo, Ming .

NATURE, 2006, 441 (7097) :1162-1166

[4] Loss of PINK1 Function Promotes Mitophagy through Effects on Oxidative Stress and Mitochondrial Fission [J].

Dagda, Ruben K. ;

Cherra, Salvatore J., III ;

Kulich, Scott M. ;

Tandon, Anurag ;

Park, David ;

Chu, Charleen T. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (20) :13843-13855

[5] Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin [J].

Exner, Nicole ;

Treske, Bettina ;

Paquet, Dominik ;

Holmström, Kira ;

Schiesling, Carola ;

Gispert, Suzana ;

Carballo-Carbajal, Iria ;

Berg, Daniela ;

Hoepken, Hans-Hermann ;

Gasser, Thomas ;

Kr ger, Rejko ;

Winklhofer, Konstanze F. ;

Vogel, Frank ;

Reichert, Andreas S. ;

Auburger, Georg ;

Kahle, Philipp J. ;

Schmid, Bettina ;

Haass, Christian .

JOURNAL OF NEUROSCIENCE, 2007, 27 (45) :12413-12418

[6] Leucine-rich repeat kinase 2 associates with lipid rafts [J].

Hatano, Taku ;

Kubo, Shin-ichiro ;

Imai, Satoshi ;

Maeda, Masahiro ;

Ishikawa, Kiyoshi ;

Mizuno, Yoshikuni ;

Hattori, Nobutaka .

HUMAN MOLECULAR GENETICS, 2007, 16 (06) :678-690

[7] Novel PINK1 mutations in early-onset parkinsonism [J].

Hatano, Y ;

Li, YZ ;

Sato, K ;

Asakawa, S ;

Yamamura, Y ;

Tomiyama, H ;

Yoshino, H ;

Asahina, M ;

Kobayashi, S ;

Hassin-Baer, S ;

Lu, CS ;

Ng, AR ;

Rosales, RL ;

Shimizu, N ;

Toda, T ;

Mizuno, Y ;

Hattori, N .

ANNALS OF NEUROLOGY, 2004, 56 (03) :424-427

[8] LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing [J].

Kabeya, Y ;

Mizushima, N ;

Uero, T ;

Yamamoto, A ;

Kirisako, T ;

Noda, T ;

Kominami, E ;

Ohsumi, Y ;

Yoshimori, T .

EMBO JOURNAL, 2000, 19 (21) :5720-5728

[9] PINK1 controls mitochondrial localization of Parkin through direct phosphorylation [J].

Kim, Yongsung ;

Park, Jeehye ;

Kim, Sunhong ;

Song, Saera ;

Won, Seok-Kyu ;

Lee, Sang-Hee ;

Kitada, Tohru ;

Kim, Jin-Man ;

Chung, Jongkyeong .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 377 (03) :975-980

[10] Parkin is recruited selectively to impaired mitochondria and promotes their autophagy [J].

Narendra, Derek ;

Tanaka, Atsushi ;

Suen, Der-Fen ;

Youle, Richard J. .

JOURNAL OF CELL BIOLOGY, 2008, 183 (05) :795-803

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