PINK1 Stabilized by Mitochondrial Depolarization Recruits Parkin to Damaged Mitochondria and Activates Latent Parkin for Mitophagy

DSpace/Manakin Repository

PINK1 Stabilized by Mitochondrial Depolarization Recruits Parkin to Damaged Mitochondria and Activates Latent Parkin for Mitophagy

Citable link to this page

 

 
Title: PINK1 Stabilized by Mitochondrial Depolarization Recruits Parkin to Damaged Mitochondria and Activates Latent Parkin for Mitophagy
Author: Matsuda, Noriyuki; Sato, Shigeto; Shiba, Kahori; Okatsu, Kei; Saisho, Keiko; Sou, Yu-shin; Saiki, Shinji; Kawajiri, Sumihiro; Sato, Fumiaki; Kimura, Mayumi; Komatsu, Masaaki; Hattori, Nobutaka; Tanaka, Keiji; Gautier, Clement A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Matsuda, Noriyuki, Shigeto Sato, Kahori Shiba, Kei Okatsu, Keiko Saisho, Clement A. Gautier, Yu-shin Sou, et al. 2010. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. The Journal of Cell Biology 189(2): 211-221.
Full Text & Related Files:
Abstract: Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Recent identification of genes linked to familial forms of PD such as Parkin and PINK1 (PTEN-induced putative kinase 1) has revealed that ubiquitylation and mitochondrial integrity are key factors in disease pathogenesis. However, the exact mechanism underlying the functional interplay between Parkin-catalyzed ubiquitylation and PINK1-regulated mitochondrial quality control remains an enigma. In this study, we show that PINK1 is rapidly and constitutively degraded under steady-state conditions in a mitochondrial membrane potential–dependent manner and that a loss in mitochondrial membrane potential stabilizes PINK1 mitochondrial accumulation. Furthermore, PINK1 recruits Parkin from the cytoplasm to mitochondria with low membrane potential to initiate the autophagic degradation of damaged mitochondria. Interestingly, the ubiquitin ligase activity of Parkin is repressed in the cytoplasm under steady-state conditions; however, PINK1-dependent mitochondrial localization liberates the latent enzymatic activity of Parkin. Some pathogenic mutations of PINK1 and Parkin interfere with the aforementioned events, suggesting an etiological importance. These results provide crucial insight into the pathogenic mechanisms of PD.
Published Version: doi:10.1083/jcb.200910140
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856912/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4942623
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters