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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-5-25
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-10094049, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-10625663, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-10652318, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-11110793, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-11427728, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-11948617, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-12021262, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-12177198, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-14607334, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-14665635, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-14722078, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15087508, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15181200, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15292218, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15349870, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15611723, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-15824318, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16009891, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16079129, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16200196, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16207731, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16226715, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16517609, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16543934, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16547921, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16672980, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16672981, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16700027, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16702191, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16769864, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16818890, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-16938835, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-17000703, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-17062640, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-17638420, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-2154259, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-2566813, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-7687266, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-7876093, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-8756626, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-9027314, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579517-9761807
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1545-7885
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e172
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17579517-Animals, pubmed-meshheading:17579517-Apoptosis, pubmed-meshheading:17579517-Base Sequence, pubmed-meshheading:17579517-Cytochromes c, pubmed-meshheading:17579517-HSP90 Heat-Shock Proteins, pubmed-meshheading:17579517-HeLa Cells, pubmed-meshheading:17579517-Humans, pubmed-meshheading:17579517-Mitochondria, pubmed-meshheading:17579517-Oxidative Stress, pubmed-meshheading:17579517-PC12 Cells, pubmed-meshheading:17579517-Parkinsonian Disorders, pubmed-meshheading:17579517-Phosphorylation, pubmed-meshheading:17579517-Point Mutation, pubmed-meshheading:17579517-Protein Binding, pubmed-meshheading:17579517-Protein Kinases, pubmed-meshheading:17579517-RNA, Small Interfering, pubmed-meshheading:17579517-Rats, pubmed-meshheading:17579517-Recombinant Proteins, pubmed-meshheading:17579517-Substrate Specificity, pubmed-meshheading:17579517-Transfection
pubmed:year
2007
pubmed:articleTitle
PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1.
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