RGD Reference Report - PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. - Rat Genome Database

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PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1.

Authors: Pridgeon, JW  Olzmann, JA  Chin, LS  Li, L 
Citation: Pridgeon JW, etal., PLoS Biol. 2007 Jul;5(7):e172. Epub 2007 Jun 19.
RGD ID: 8693356
Pubmed: PMID:17579517   (View Abstract at PubMed)
PMCID: PMC1892574   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pbio.0050172   (Journal Full-text)

Mutations in the PTEN induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). So far, no substrates of PINK1 have been reported, and the mechanism by which PINK1 mutations lead to neurodegeneration is unknown. Here we report the identification of TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone also known as heat shock protein 75 (Hsp75), as a cellular substrate for PINK1 kinase. PINK1 binds and colocalizes with TRAP1 in the mitochondria and phosphorylates TRAP1 both in vitro and in vivo. We show that PINK1 protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria, and this protective action of PINK1 depends on its kinase activity to phosphorylate TRAP1. Moreover, we find that the ability of PINK1 to promote TRAP1 phosphorylation and cell survival is impaired by PD-linked PINK1 G309D, L347P, and W437X mutations. Our findings suggest a novel pathway by which PINK1 phosphorylates downstream effector TRAP1 to prevent oxidative-stress-induced apoptosis and implicate the dysregulation of this mitochondrial pathway in PD pathogenesis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrial inner membrane located_inIDA 8693356; 8693356PMID:17579517ParkinsonsUK-UCL 
mitochondrial intermembrane space located_inIDA 8693356; 8693356PMID:17579517ParkinsonsUK-UCL 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Pink1  (PTEN induced kinase 1)
Trap1  (TNF receptor-associated protein 1)


Additional Information