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

Kawajiri, Sumihiro; Saiki, Shinji; Sato, Shigeto; Sato, Fumiaki; Hatano, Taku; Eguchi, Hiroto; Hattori, Nobutaka

doi:10.1016/j.febslet.2010.02.016

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Volume 584, Issue 6 , Pages 1073-1079, 19 March 2010

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

Edited by Jesus Avila

Sumihiro Kawajiri
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Joint first authors.
Shinji Saiki
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Joint first authors.
Shigeto Sato
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Fumiaki Sato
- Research Institute for Disease of Old Age, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Taku Hatano
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Hiroto Eguchi
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Nobutaka Hattori
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Corresponding author. Address: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Fax: +81 3 5800 0547.

Received 16 December 2009; received in revised form 29 January 2010; accepted 2 February 2010. published online 11 February 2010.

Abstract

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)

Keywords: PTEN-induced putative kinase 1, Parkin, Mitophagy, Autophagy, Parkinson’s disease

Abbreviations: CCCP, carbonyl cyanide m-chlorophenylhydrazone, 3-MA, 3-methyladenine, MEFs, mouse embryonic fibroblasts, MTS, mitochondrial targeting sequence, PD, Parkinson’s disease, PINK1, PTEN-induced putative kinase 1, UPS, ubiquitin–proteasome system