Murata H, Sakaguchi M, Kataoka K, Huh NH

Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson's disease. Recent works have suggested 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 ...

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this study, we found that PINK1 forms a complex with SARM1 and 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 adaptor protein for Toll-like receptor, bound to PINK1 and promoted TRAF6-mediated lysine-63 chain ubiquitination of PINK1 at lysine 433. Down-regulation of SARM1 and TRAF6 abrogated accumulation of PINK1 followed by recruitment of Parkin to damaged mitochondria. Some pathogenic mutations of PINK1 reduce the complex formation and ubiqutination. These results indicate that the association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy.

Date: Jul. 24, 2013

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