SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria
Open Access
- 15 September 2013
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 24 (18), 2772-2784
- https://doi.org/10.1091/mbc.e13-01-0016
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.Keywords
This publication has 65 references indexed in Scilit:
- Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegansDevelopment, 2011
- Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphologyThe Journal of cell biology, 2011
- Broad activation of the ubiquitin–proteasome system by Parkin is critical for mitophagyHuman Molecular Genetics, 2011
- SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to humanMolecular Immunology, 2008
- Parkinsonism genes: culprits and cluesJournal of Neurochemistry, 2006
- Early-onset parkinsonism associated with PINK1 mutationsNeurology, 2005
- Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stabilityProceedings of the National Academy of Sciences of the United States of America, 2005
- A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signalingPublished by Cold Spring Harbor Laboratory ,2004
- Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset ParkinsonismScience, 2003
- TRAF6 is a signal transducer for interleukin-1Nature, 1996