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SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771941/ https://www.ncbi.nlm.nih.gov/pubmed/23885119 http://dx.doi.org/10.1091/mbc.E13-01-0016 |
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author | Murata, Hitoshi Sakaguchi, Masakiyo Kataoka, Ken Huh, Nam-ho |
author_facet | Murata, Hitoshi Sakaguchi, Masakiyo Kataoka, Ken Huh, Nam-ho |
author_sort | Murata, Hitoshi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3771941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-37719412013-11-30 SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria Murata, Hitoshi Sakaguchi, Masakiyo Kataoka, Ken Huh, Nam-ho Mol Biol Cell Articles 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. The American Society for Cell Biology 2013-09-15 /pmc/articles/PMC3771941/ /pubmed/23885119 http://dx.doi.org/10.1091/mbc.E13-01-0016 Text en © 2013 Murata et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Murata, Hitoshi Sakaguchi, Masakiyo Kataoka, Ken Huh, Nam-ho SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title | SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title_full | SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title_fullStr | SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title_full_unstemmed | SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title_short | SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria |
title_sort | sarm1 and traf6 bind to and stabilize pink1 on depolarized mitochondria |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771941/ https://www.ncbi.nlm.nih.gov/pubmed/23885119 http://dx.doi.org/10.1091/mbc.E13-01-0016 |
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