p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria

Autor: Masaaki Komatsu, Shigeto Sato, Keiko Saisho, Yu-shin Sou, Mayumi Kimura, Kei Okatsu, Noriyuki Matsuda, Midori Shimanuki, Hiroshi Shitara, Nobutaka Hattori, Kazuto Nakada, Keiji Tanaka
Rok vydání: 2010
Předmět:
Zdroj: Genes to Cells.
ISSN: 1365-2443
1356-9597
Popis: PINK1 and Parkin were first identified as the causal genes responsible for familial forms of early-onset Parkinson’s disease (PD), a prevalent neurodegenerative disorder. PINK1 encodes a mitochondrial serine/threonine protein kinase, whereas Parkin encodes an ubiquitin-protein ligase. PINK1 and Parkin cooperate to maintain mitochondrial integrity; however, the detailed molecular mechanism of how Parkin-catalyzed ubiquitylation results in mitochondrial integrity remains an enigma. In this study, we show that Parkin-catalyzed K63-linked polyubiquitylation of depolarized mitochondria resulted in ubiquitylated mitochondria being transported along microtubules to cluster in the perinuclear region, which was interfered by pathogenic mutations of Parkin. In addition, p62/SQSTM1 (hereafter referred to as p62) was recruited to depolarized mitochondria after Parkin-directed ubiquitylation. Intriguingly, deletion of p62 in mouse embryonic fibroblasts resulted in a gross loss of mitochondrial perinuclear clustering but did not hinder mitochondrial degradation. Thus, p62 is required for ubiquitylation-dependent clustering of damaged mitochondria, which resembles p62-mediated ‘aggresome’ formation of misfolded/unfolded proteins after ubiquitylation.
Databáze: OpenAIRE
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