SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria

Hitoshi Murata, Masakiyo Sakaguchi, Ken Kataoka, Nam Ho Huh

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson's disease. Recent work suggests that loss of mitochondrial membrane potential stabilizes PINK1 and that accumulated PINK1 recruits parkin from the cytoplasm to mitochondria for elimination of depolarized mitochondria, which is known as mitophagy. In this study, we find that PINK1 forms a complex with sterile α and TIR motif containing 1 (SARM1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which is important for import of PINK1 in the outer membrane and stabilization of PINK1 on depolarized mitochondria. SARM1, which is known to be an adaptor protein for Toll-like receptor, binds to PINK1 and promotes TRAF6-mediated lysine 63 chain ubiquitination of PINK1 at lysine 433. Down-regulation of SARM1 and TRAF6 abrogates accumulation of PINK1, followed by recruitment of parkin to damaged mitochondria. Some pathogenic mutations of PINK1 reduce the complex formation and ubiquitination. These results indicate that association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy.

Original languageEnglish
Pages (from-to)2772-2784
Number of pages13
JournalMolecular Biology of the Cell
Volume24
Issue number18
DOIs
Publication statusPublished - Sep 15 2013

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Mitochondria
Mitochondrial Degradation
Ubiquitination
Lysine
PTEN-induced putative kinase
Mutation
Mitochondrial Membrane Potential
Toll-Like Receptors
Parkinson Disease
Cytoplasm

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria. / Murata, Hitoshi; Sakaguchi, Masakiyo; Kataoka, Ken; Huh, Nam Ho.

In: Molecular Biology of the Cell, Vol. 24, No. 18, 15.09.2013, p. 2772-2784.

Research output: Contribution to journalArticle

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