title: 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.
authors.affiliation: Department of Neurology, Columbia University, 650 West 168th Street, New York, NY 10032, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shao
authors.forename: Jessica
authors.initials: J
authors.lastname: May
authors.forename: Delphine
authors.initials: D
authors.lastname: Prou
authors.forename: Celine
authors.initials: C
authors.lastname: Perier
authors.forename: William
authors.initials: W
authors.lastname: Dauer
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000201:enzymology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000201:enzymology; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase