title: Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential.
abstract: Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and that Klokin 1 may compensate for Parkin deficiency.
authors.affiliation: Department of Clinical Research, Tokushima National Hospital, National Hospital Organization, 1354 Shikiji, Kamojima, Yoshinogawa, Tokushima 776-8585, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Wataru
authors.initials: W
authors.lastname: Sako
authors.forename: Satoshi
authors.initials: S
authors.lastname: Goto
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Sawada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uchida
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Kagawa
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.forename: Takao
authors.initials: T
authors.lastname: Mitsui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D017350:N-Acetylgalactosaminyltransferases; C412725:chondroitin synthase