L347P PINK1 mutant that fails to bind to Hsp90/Cdc37 chaperones is rapidly degraded in a proteasome-dependent manner

Yasuhiro Moriwaki, Yeon Jeong Kim, Yukari Ido, Hidemi Misawa, Koichiro Kawashima, Shogo Endo, Ryosuke Takahashi

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Mutation of PTEN-induced kinase 1 (PINK1), which encodes a putative mitochondrial serine/threonine kinase, leads to PARK6, an autosomal recessive form of familial Parkinson's disease. Although the precise function(s) of PINK1 protein is unknown, the recessive inheritance of this form of Parkinson's disease suggests loss of PINK1 function is closely associated with its pathogenesis. Here we report that PINK1 forms a complex with the molecular chaperones Hsp90 and Cdc37/p50 within cells, which appears to enhance its stability. When cells were treated with an Hsp90 inhibitor (geldanamycin or novobiocin), levels of PINK1 were greatly diminished, reflecting its rapid degradation via ubiquitin-proteasome pathway. Similarly, the half-life of a pathogenic PINK1 mutant (L347P) that did not interact with Hsp90 or Cdc37/p50 was only 30 min, whereas that of wild-type PINK1 was 1 h. These results strongly suggest that Hsp90 and Cdc37 are binding partners of PINK1 which regulate its stability.

Original languageEnglish
Pages (from-to)43-48
Number of pages6
JournalNeuroscience Research
Issue number1
Publication statusPublished - 2008 May 1



  • Cdc37
  • Hsp90
  • PINK1
  • Parkinson's disease
  • Proteasome
  • Stability

ASJC Scopus subject areas

  • Neuroscience(all)

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