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The kinase domain of mitochondrial PINK1 faces the cytoplasm.

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.

SUBMITTER: Zhou C

PROVIDER: S-EPMC2575334 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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The kinase domain of mitochondrial PINK1 faces the cytoplasm.

Zhou Chun C Huang Yong Y Shao Yufang Y May Jessica J Prou Delphine D Perier Celine C Dauer William W Schon Eric A EA Przedborski Serge S

Proceedings of the National Academy of Sciences of the United States of America 20080807 33

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 t ...[more]

PMID: 18687899

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