The kinase domain of mitochondrial PINK1 faces the cytoplasm

Chun Zhou, Yong Huang, Yufang Shao, Jessica May, Delphine Prou, Celine Perier, William Dauer, Eric A. Schon, Serge Przedborski

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of autosomal recessive familial Parkinson's disease (PD). Efforts in deducing the PINK1 signaling pathway have been hindered by controversy around its subcellular and submitochondrial localization and the authenticity of its reported substrates. We show here that this mitochondrial protein exhibits a topology in which the kinase domain faces the cytoplasm and the N-terminal tail is inside the mitochondria. Although deletion of the transmembrane domain disrupts this topology, common PD-linked PINK1 mutations do not. These results are critical in rectifying the location and orientation of PINK1 in mitochondria, and they should help decipher its normal physiological function and potential pathogenic role in PD.

Original languageEnglish (US)
Pages (from-to)12022-12027
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number33
DOIs
StatePublished - Aug 19 2008
Externally publishedYes

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Cytoplasm
Phosphotransferases
Parkinson Disease
Mitochondria
Mutation
Mitochondrial Proteins
Parkinsonian Disorders
PTEN-induced putative kinase

Keywords

  • Mitochondria
  • Parkin
  • Parkinson's disease
  • Topology

ASJC Scopus subject areas

  • General

Cite this

The kinase domain of mitochondrial PINK1 faces the cytoplasm. / Zhou, Chun; Huang, Yong; Shao, Yufang; May, Jessica; Prou, Delphine; Perier, Celine; Dauer, William; Schon, Eric A.; Przedborski, Serge.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 33, 19.08.2008, p. 12022-12027.

Research output: Contribution to journalArticle

Zhou, C, Huang, Y, Shao, Y, May, J, Prou, D, Perier, C, Dauer, W, Schon, EA & Przedborski, S 2008, 'The kinase domain of mitochondrial PINK1 faces the cytoplasm', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 33, pp. 12022-12027. https://doi.org/10.1073/pnas.0802814105
Zhou, Chun ; Huang, Yong ; Shao, Yufang ; May, Jessica ; Prou, Delphine ; Perier, Celine ; Dauer, William ; Schon, Eric A. ; Przedborski, Serge. / The kinase domain of mitochondrial PINK1 faces the cytoplasm. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 33. pp. 12022-12027.
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