title: Tom70 is essential for PINK1 import into mitochondria.
abstract: PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a responsible gene of Parkinson's disease (PD). The precursor of PINK1 is synthesized in the cytosol and then imported into the mitochondria via the translocase of the OMM (TOM) complex. However, a large part of PINK1 import mechanism remains unclear. In this study, we examined using cell-free system the mechanism by which PINK1 is targeted to and assembled into mitochondria. Surprisingly, the main component of the import channel, Tom40 was not necessary for PINK1 import. Furthermore, we revealed that the import receptor Tom70 is essential for PINK1 import. In addition, we observed that although PINK1 has predicted mitochondrial targeting signal, it was not processed by the mitochondrial processing peptidase. Thus, our results suggest that PINK1 is imported into mitochondria by a unique pathway that is independent of the TOM core complex but crucially depends on the import receptor Tom70.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany. hmg1@tokyo-med.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Qiping
authors.initials: Q
authors.lastname: Lu
authors.forename: Doron
authors.initials: D
authors.lastname: Rapaport
authors.forename: Vera
authors.initials: V
authors.lastname: Kozjak-Pavlovic
mesh_terms: D000818:Animals; D002474:Cell-Free System; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010447:Peptide Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010447:Peptide Hydrolases; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C402118:TOMM70 protein, human; C559261:Tom70 protein, mouse