2022/11/25 更新

写真b

オカ トシヒコ
岡 敏彦
OKA Toshihiko
*大学が定期的に情報更新している項目(その他は、researchmapの登録情報を転載)
所属*
理学部 生命理学科
理学研究科 生命理学専攻 博士課程後期課程
理学研究科 生命理学専攻 博士課程前期課程
職名*
教授
学位
博士(理学) ( 東京大学 )
研究テーマ*
  • 細胞小器官(オルガネラ)はそれぞれ固有の機能と形態をもっている。オルガネラの機能は細胞の生存にとって必須だが、オルガネラの形態は細胞やオルガネラの機能にとってどのような役割があるのか?この命題を、細胞内のエネルギー産生の場であるミトコンドリアに着目し、分子生物学や生化学的手法を用いて、その膜形態の形成と制御機構を理解することで、オルガネラ形態の生理的意義の解明をめざしている。

  • 学内職務経歴*
    • 2012年4月 - 現在 
      理学部   生命理学科   教授
    • 2012年4月 - 現在 
      理学研究科   生命理学専攻 博士課程前期課程   教授
    • 2012年4月 - 現在 
      理学研究科   生命理学専攻 博士課程後期課程   教授
     

    研究分野

    • ライフサイエンス / 細胞生物学

    経歴

    • 2012年4月 - 現在 
      立教大学   理学研究科 生命理学専攻博士課程前期課程   教授

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    • 2012年4月 - 現在 
      立教大学   理学研究科 生命理学専攻博士課程後期課程   教授

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    • 2012年4月 - 現在 
      立教大学   理学部 生命理学科   教授

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    学歴

    • 1991年4月 - 1994年3月 
      東京大学   理学系研究科   植物学専攻

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      国名: 日本国

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    • 1991年4月 - 1994年3月 
      東京大学   理学系研究科   植物学専攻

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      国名: 日本国

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    • 1989年4月 - 1991年3月 
      東京大学   理学系研究科   植物学専攻

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      国名: 日本国

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    • 1989年4月 - 1991年3月 
      東京大学   理学系研究科   植物学専攻

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      国名: 日本国

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    • 1985年4月 - 1989年3月 
      九州大学   理学部   生物学科

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      国名: 日本国

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    論文

    • Localization of myoglobin in mitochondria: implication in regulation of mitochondrial respiration in rat skeletal muscle 査読有り 国際誌

      Rikuhide Koma, Tsubasa Shibaguchi, Claudia Pérez López, Toshihiko Oka, Thomas Jue, Hisashi Takakura, Kazumi Masuda

      Physiological Reports9 ( 5 ) e14769   2021年3月

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      記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

      Mitochondria play a principal role in metabolism, and mitochondrial respiration is an important process for producing adenosine triphosphate. Recently, we showed the possibility that the muscle-specific protein myoglobin (Mb) interacts with mitochondrial complex IV to augment the respiration capacity in skeletal muscles. However, the precise mechanism for the Mb-mediated upregulation remains under debate. The aim of this study was to ascertain whether Mb is truly integrated into the mitochondria of skeletal muscle and to investigate the submitochondrial localization. Isolated mitochondria from rat gastrocnemius muscle were subjected to different proteinase K (PK) concentrations to digest proteins interacting with the outer membrane. Western blotting analysis revealed that the PK digested translocase of outer mitochondrial membrane 20 (Tom20), and the immunoreactivity of Tom20 decreased with the amount of PK used. However, the immunoreactivity of Mb with PK treatment was better preserved, indicating that Mb is integrated into the mitochondria of skeletal muscle. The mitochondrial protease protection assay experiments suggested that Mb localizes within the mitochondria in the inner membrane from the intermembrane space side. These results strongly suggest that Mb inside muscle mitochondria could be implicated in the regulation of mitochondrial respiration via complex IV.

      DOI: 10.14814/phy2.14769

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      その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.14814/phy2.14769

    • The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain 査読有り

      Seiko Nakamura, Aiko Matsui, Shiori Akabane, Yasushi Tamura, Azumi Hatano, Yuriko Miyano, Hiroshi Omote, Mizuho Kajikawa, Katsumi Maenaka, Yoshinori Moriyama, Toshiya Endo, Toshihiko Oka

      Communications Biology3 ( 1 )   2020年12月

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      担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

      Abstract

      LETM1 is a mitochondrial inner membrane protein that is required for maintaining the mitochondrial morphology and cristae structures, and regulates mitochondrial ion homeostasis. Here we report a role of LETM1 in the organization of cristae structures. We identified four amino acid residues of human LETM1 that are crucial for complementation of the growth deficiency caused by gene deletion of a yeast LETM1 orthologue. Substituting amino acid residues with alanine disrupts the correct assembly of a protein complex containing LETM1 and prevents changes in the mitochondrial morphology induced by exogenous LETM1 expression. Moreover, the LETM1 protein changes the shapes of the membranes of in vitro-reconstituted proteoliposomes, leading to the formation of invaginated membrane structures on artificial liposomes. LETM1 mutant proteins with alanine substitutions fail to facilitate the formation of invaginated membrane structures, suggesting that LETM1 plays a fundamental role in the organization of mitochondrial membrane morphology.

      DOI: 10.1038/s42003-020-0832-5

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      その他リンク: http://www.nature.com/articles/s42003-020-0832-5

    • In vitro synthesis of the human calcium transporter Letm1 within cell-sized liposomes and investigation of its lipid dependency 査読有り

      Okamura, K, S. Matsushita, Y. Kato, H. Watanabe, A. Matsui, T. Oka, T. Matsuura

      J. Biosci. Bioeng.127 ( 5 ) 544 - 548   2019年5月

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      DOI: 10.1016/j.jbiosc.2018.11.003

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    • Concentration of mitochondrial DNA mutations by cytoplasmic transfer from platelets to cultured mouse cells. 査読有り

      Ishikawa, K, K. Kobayashi, A. Yamada, M. Umehara, T. Oka, K. Nakada

      PLOS ONE   2019年

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      DOI: 10.1371/journal.pone.0213283

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    • Inactivation of cardiolipin synthase triggers changes in mitochondrial morphology 査読有り

      Matsumura, A, Higuchi, J, Watanabe, Y, Kato, M, Aoki, K, Akabane, S, Endo, T, Oka, T

      FEBS Letters592 ( 2 ) 209 - 218   2018年1月1日

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley Blackwell  

      Mitochondrial tubular structures are maintained by a balance between membrane fusion and fission that is regulated by various factors, including Drp1 and mitofusin/fzo-1. Here we report the role of cardiolipin (CL) synthase in the regulation of mitochondrial morphology. Knockdown of CL synthase induced mitochondrial elongation in nematode and human cells. Knockdown of both nematode cardiolipin synthase and drp-1 or fzo-1 suggested that knocking down CL synthase decreases mitochondrial division. Mass spectrometric analysis of human CL synthase-knocked down cells revealed a decreased amount of CL and an accumulation of phosphatidylglycerol, a CL precursor. Knockdown of other genes involved in CL synthesis did not influence mitochondrial morphology. Thus, mitochondrial elongation may result from the accumulation of phosphatidylglycerol rather than decreased CL.

      DOI: 10.1002/1873-3468.12948

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    • Structural insights into ubiquitin phosphorylation by PINK1 査読有り 国際誌

      Okatsu, K, Y. Sato, K. Yamano, N. Matsuda, L. Negishi, A. Takahashi, A. Yamagata, S. Goto-Ito, M. Mishima, Y. Ito, T. Oka, K. Tanaka, S. Fukai

      Sci. Rep.8 ( 1 ) 10382 - 10382   2018年

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      DOI: 10.1038/s41598-018-28656-8

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    • Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin. 査読有り 国際誌

      Tadato Ban, Takaya Ishihara, Hiroto Kohno, Shotaro Saita, Ayaka Ichimura, Katsumi Maenaka, Toshihiko Oka, Katsuyoshi Mihara, Naotada Ishihara

      Nature cell biology19 ( 7 ) 856 - 863   2017年7月

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. Optic atrophy 1 (OPA1) is an essential GTPase protein for both mitochondrial inner membrane (IM) fusion and cristae morphology. Under mitochondria-stress conditions, membrane-anchored L-OPA1 is proteolytically cleaved to form peripheral S-OPA1, leading to the selection of damaged mitochondria for mitophagy. However, molecular details of the selective mitochondrial fusion are less well understood. Here, we showed that L-OPA1 and cardiolipin (CL) cooperate in heterotypic mitochondrial IM fusion. We reconstituted an in vitro membrane fusion reaction using purified human L-OPA1 protein expressed in silkworm, and found that L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion. GTP-independent membrane tethering through L-OPA1 and CL primes the subsequent GTP-hydrolysis-dependent fusion, which can be modulated by the presence of S-OPA1. These results unveil the most minimal intracellular membrane fusion machinery. In contrast, independent of CL, a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure. Thus, multiple OPA1 functions are modulated by local CL conditions for regulation of mitochondrial morphology and quality control.

      DOI: 10.1038/ncb3560

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    • Constitutive Activation of PINK1 Protein Leads to Proteasome-mediated and Non-apoptotic Cell Death Independently of Mitochondrial Autophagy 査読有り

      Shiori Akabane, Kohei Matsuzaki, Shun-ichi Yamashita, Kana Arai, Kei Okatsu, Tomotake Kanki, Noriyuki Matsuda, Toshihiko Oka

      JOURNAL OF BIOLOGICAL CHEMISTRY291 ( 31 ) 16162 - 16174   2016年7月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

      Phosphatase and tensin homolog-induced putative kinase 1 (PINK1), a Ser/Thr kinase, and PARKIN, a ubiquitin ligase, are causal genes for autosomal recessive early-onset parkinsonism. Multiple lines of evidence indicate that PINK1 and PARKIN cooperatively control the quality of the mitochondrial population via selective degradation of damaged mitochondria by autophagy. Here, we report that PINK1 and PARKIN induce cell death with a 12-h delay after mitochondrial depolarization, which differs from the time profile of selective autophagy of mitochondria. This type of cell death exhibited definite morphologic features such as plasma membrane rupture, was insensitive to a pan-caspase inhibitor, and did not involve mitochondrial permeability transition. Expression of a constitutively active form of PINK1 caused cell death in the presence of a pan-caspase inhibitor, irrespective of the mitochondrial membrane potential. PINK1-mediated cell death depended on the activities of PARKIN and proteasomes, but it was not affected by disruption of the genes required for autophagy. Furthermore, fluorescence and electron microscopic analyses revealed that mitochondria were still retained in the dead cells, indicating that PINK1-mediated cell death is not caused by mitochondrial loss. Our findings suggest that PINK1 and PARKIN play critical roles in selective cell death in which damaged mitochondria are retained, independent of mitochondrial autophagy.

      DOI: 10.1074/jbc.M116.714923

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    • PKA Regulates PINK1 Stability and Parkin Recruitment to Damaged Mitochondria through Phosphorylation of MIC60 査読有り

      Shiori Akabane, Midori Uno, Naoki Tani, Shunta Shimazaki, Natsumi Ebara, Hiroki Kato, Hidetaka Kosako, Toshihiko Oka

      MOLECULAR CELL62 ( 3 ) 371 - 384   2016年5月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

      A mitochondrial kinase, PTEN-induced putative kinase 1 (PINK1), selectively recruits the ubiquitin ligase Parkin to damaged mitochondria, which modifies mitochondria by polyubiquitination, leading to mitochondrial autophagy. Here, we report that treatment with an adenylate cyclase agonist or expression of protein kinase A (PKA) impairs Parkin recruitment to damaged mitochondria and decreases PINK1 protein levels. We identified a mitochondrial membrane protein, MIC60 (also known as mitofilin), as a PKA substrate. Mutational and mass spectrometric analyses revealed that the Ser528 residue of MIC60 undergoes PKA-dependent phosphorylation. MIC60 transiently interacts with PINK1, and MIC60 downregulation leads to a reduction in PINK1 and mislocalization of Parkin. Phosphorylation-mimic mutants of MIC60 fail to restore the defect in Parkin recruitment in MIC60-knocked down cells, whereas a phosphorylation-deficient MIC60 mutant facilitates the mitochondrial localization of Parkin. Our findings indicate that PKA-mediated phosphorylation of MIC60 negatively regulates mitochondrial clearance that is initiated by PINK1 and Parkin.

      DOI: 10.1016/j.molcel.2016.03.037

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    • Unconventional PINK1 localization to the outer membrane of depolarized mitochondria drives Parkin recruitment 査読有り

      Kei Okatsu, Mayumi Kimura, Toshihiko Oka, Keiji Tanaka, Noriyuki Matsuda

      JOURNAL OF CELL SCIENCE128 ( 5 ) 964 - 978   2015年3月

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      記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

      Dysfunction of PTEN-induced putative kinase 1 (PINK1), a Ser/Thr kinase with an N-terminal mitochondrial-targeting sequence (MTS), causes familial recessive parkinsonism. Reduction of the mitochondrial membrane potential limits MTS-mediated matrix import and promotes PINK1 accumulation on the outer mitochondrial membrane (OMM) of depolarized mitochondria. PINK1 then undergoes autophosphorylation and phosphorylates ubiquitin and Parkin, a cytosolic ubiquitin ligase, for clearance of damaged mitochondria. The molecular basis for PINK1 localization on the OMM of depolarized mitochondria rather than release to the cytosol is poorly understood. Here, we disentangle the PINK1 localization mechanism using deletion mutants and a newly established constitutively active PINK1 mutant. Disruption of the MTS through N-terminal insertion of aspartic acid residues results in OMM localization of PINK1 in energized mitochondria. Unexpectedly, the MTS and putative transmembrane domain (TMD) are dispensable for OMM localization, whereas mitochondrial translocase Tom40 (also known as TOMM40) and an alternative mitochondrial localization signal that resides between the MTS and TMD are required. PINK1 utilizes a mitochondrial localization mechanism that is distinct from that of conventional MTS proteins and that presumably functions in conjunction with the Tom complex in OMM localization when the conventional N-terminal MTS is inhibited.

      DOI: 10.1242/jcs.161000

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    • A dimeric pink1-containing complex on depolarized mitochondria stimulates parkin recruitment 査読有り

      Kei Okatsu, Midori Uno, Fumika Koyano, Etsu Go, Mayumi Kimura, Toshihiko Oka, Keiji Tanaka, Noriyuki Matsuda

      Journal of Biological Chemistry288 ( 51 ) 36372 - 36384   2013年12月20日

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      Parkinsonism typified by sporadic Parkinson disease is a prevalent neurodegenerative disease. Mutations in PINK1 (PTENinduced putative kinase 1), a mitochondrial Ser/Thr protein kinase, or PARKIN, a ubiquitin-protein ligase, cause familial parkinsonism. The accumulation and autophosphorylation of PINK1 on damaged mitochondria results in the recruitment of Parkin, which ultimately triggers quarantine and/or degradation of the damaged mitochondria by the proteasome and autophagy. However, the molecular mechanism of PINK1 in dissipation of the mitochondrial membrane potential (ΔΨm) has not been fully elucidated. Here we show by fluorescence-based techniques that the PINK1 complex formed following a decrease in ΔΨm is composed of two PINK1 molecules and is correlated with intermolecular phosphorylation of PINK1. Disruption of complex formation by the PINK1 S402A mutation weakened Parkin recruitment onto depolarized mitochondria. The most disease-relevant mutations of PINK1 inhibit the complex formation. Taken together, these results suggest that formation of the complex containing dyadic PINK1 is an important step for Parkin recruitment onto damaged mitochondria. © 2013 by The American Society for Biochemistry and Molecular Biology.

      DOI: 10.1074/jbc.M113.509653

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    • Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology. 査読有り 国際誌

      Kenta Onoue, Akihiro Jofuku, Reiko Ban-Ishihara, Takaya Ishihara, Maki Maeda, Takumi Koshiba, Takashi Itoh, Mitsunori Fukuda, Hidenori Otera, Toshihiko Oka, Hiroyoshi Takano, Noboru Mizushima, Katsuyoshi Mihara, Naotada Ishihara

      Journal of cell science126 ( Pt 1 ) 176 - 85   2013年1月1日

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      記述言語:英語   掲載種別:研究論文(学術雑誌)  

      In yeast, C-tail-anchored mitochondrial outer membrane protein Fis1 recruits the mitochondrial-fission-regulating GTPase Dnm1 to mitochondrial fission sites. However, the function of its mammalian homologue remains enigmatic because it has been reported to be dispensable for the mitochondrial recruitment of Drp1, a mammalian homologue of Dnm1. We identified TBC1D15 as a Fis1-binding protein in HeLa cell extracts. Immunoprecipitation revealed that Fis1 efficiently interacts with TBC1D15 but not with Drp1. Bacterially expressed Fis1 and TBC1D15 formed a direct and stable complex. Exogenously expressed TBC1D15 localized mainly in cytoplasm in HeLa cells, but when coexpressed with Fis1 it localized to mitochondria. Knockdown of TBC1D15 induced highly developed mitochondrial network structures similar to the effect of Fis1 knockdown, suggesting that the TBC1D15 and Fis1 are associated with the regulation of mitochondrial morphology independently of Drp1. These data suggest that Fis1 acts as a mitochondrial receptor in the recruitment of mitochondrial morphology protein in mammalian cells.

      DOI: 10.1242/jcs.111211

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    • PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria 査読有り

      Kei Okatsu, Toshihiko Oka, Masahiro Iguchi, Kenji Imamura, Hidetaka Kosako, Naoki Tani, Mayumi Kimura, Etsu Go, Fumika Koyano, Manabu Funayama, Kahori Shiba-Fukushima, Shigeto Sato, Hideaki Shimizu, Yuko Fukunaga, Hisaaki Taniguchi, Masaaki Komatsu, Nobutaka Hattori, Katsuyoshi Mihara, Keiji Tanaka, Noriyuki Matsuda

      NATURE COMMUNICATIONS3   2012年8月

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      記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

      Dysfunction of PINK1, a mitochondrial Ser/Thr kinase, causes familial Parkinson's disease (PD). Recent studies have revealed that PINK1 is rapidly degraded in healthy mitochondria but accumulates on the membrane potential (Delta Psi m)-deficient mitochondria, where it recruits another familial PD gene product, Parkin, to ubiquitylate the damaged mitochondria. Despite extensive study, the mechanism underlying the homeostatic control of PINK1 remains unknown. Here we report that PINK1 is autophosphorylated following a decrease in Delta Psi mm and that most disease-relevant mutations hinder this event. Mass spectrometric and mutational analyses demonstrate that PINK1 autophosphorylation occurs at Ser228 and Ser402, residues that are structurally clustered together. Importantly, Ala mutation of these sites abolishes autophosphorylation of PINK1 and inhibits Parkin recruitment onto depolarized mitochondria, whereas Asp (phosphorylation-mimic) mutation promotes mitochondrial localization of Parkin even though autophosphorylation was still compromised. We propose that autophosphorylation of Ser228 and Ser402 in PINK1 is essential for efficient mitochondrial localization of Parkin.

      DOI: 10.1038/ncomms2016

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    • KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells 査読有り

      Kousuke Tanaka, Yoshimi Sugiura, Ryohei Ichishita, Katsuyoshi Mihara, Toshihiko Oka

      JOURNAL OF CELL SCIENCE124 ( 14 ) 2457 - 2465   2011年7月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

      Mitochondria utilize diverse cytoskeleton-based mechanisms to control their functions and morphology. Here, we report a role for kinesin-like protein KLP6, a newly identified member of the kinesin family, in mitochondrial morphology and dynamics. An RNA interference screen using Caenorhabditis elegans led us to identify a C. elegans KLP-6 involved in maintaining mitochondrial morphology. We cloned a cDNA coding for a rat homolog of C. elegans KLP-6, which is an uncharacterized kinesin in vertebrates. A rat KLP6 mutant protein lacking the motor domain induced changes in mitochondrial morphology and significantly decreased mitochondrial motility in HeLa cells, but did not affect the morphology of other organelles. In addition, the KLP6 mutant inhibited transport of mitochondria during anterograde movement in differentiated neuro 2a cells. To date, two kinesins, KIF1B alpha and kinesin heavy chain (KHC; also known as KIF5) have been shown to be involved in the distribution of mitochondria in neurons. Expression of the kinesin heavy chain/KIF5 mutant prevented mitochondria from entering into neurites, whereas both the KLP6 and KIF1B alpha mutants decreased mitochondrial transport in axonal neurites. Furthermore, both KLP6 and KIF1B alpha bind to KBP, a KIF1-binding protein required for axonal outgrowth and mitochondrial distribution. Thus, KLP6 is a newly identified kinesin family member that regulates mitochondrial morphology and transport.

      DOI: 10.1242/jcs.086470

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    • Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L 査読有り

      Shoko Tamai, Hiroshi Iida, Sadaki Yokota, Tomoko Sayano, Shoko Kiguchiya, Naotada Ishihara, Jun-Ichi Hayashi, Katsuyoshi Mihara, Toshihiko Oka

      JOURNAL OF CELL SCIENCE121 ( 15 ) 2588 - 2600   2008年8月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

      LETM1 is located in the chromosomal region that is deleted in patients suffering Wolf-Hirschhorn syndrome; it encodes a homolog of the yeast protein Mdm38 that is involved in mitochondrial morphology. Here, we describe the LETM1-mediated regulation of the mitochondrial volume and its interaction with the mitochondrial AAA-ATPase BCS1L that is responsible for three different human disorders. LETM1 is a mitochondrial inner-membrane protein with a large domain extruding to the matrix. The LETM1 homolog LETM2 is a mitochondrial protein that is expressed preferentially in testis and sperm. LETM1 downregulation caused mitochondrial swelling and cristae disorganization, but seemed to have little effect on membrane fusion and fission. Formation of the respiratory-chain complex was impaired by LETM1 knockdown. Cells lacking mitochondrial DNA lost active respiratory chains but maintained mitochondrial tubular networks, indicating that mitochondrial swelling caused by LETM1 knockdown is not caused by the disassembly of the respiratory chains. LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex. BCS1L knockdown caused disassembly of the respiratory chains as well as LETM1 downregulation and induced distinct changes in mitochondrial morphology.

      DOI: 10.1242/jcs.026625

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    • Identification of a novel protein MICS1 that is involved in maintenance of mitochondrial morphology and apoptotic release of cytochrome c 査読有り

      Toshihiko Oka, Tomoko Sayano, Shoko Tamai, Sadaki Yokota, Hiroki Kato, Gen Fujii, Katsuyoshi Mihara

      MOLECULAR BIOLOGY OF THE CELL19 ( 6 ) 2597 - 2608   2008年6月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CELL BIOLOGY  

      Mitochondrial morphology dynamically changes in a balance of membrane fusion and fission in response to the environment, cell cycle, and apoptotic stimuli. Here, we report that a novel mitochondrial protein, MICS1, is involved in mitochondrial morphology in specific cristae structures and the apoptotic release of cytochrome c from the mitochondria. MICS1 is an inner membrane protein with a cleavable presequence and multiple transmembrane segments and belongs to the Bi-1 super family. MICS1 down-regulation causes mitochondrial fragmentation and cristae disorganization and stimulates the release of proapoptotic proteins. Expression of the anti-apoptotic protein Bcl-XL does not prevent morphological changes of mitochondria caused by MICS1 down-regulation, indicating that MICS1 plays a role in maintaining mitochondrial morphology separately from the function in apoptotic pathways. MICS1 overproduction induces mitochondrial aggregation and partially inhibits cytochrome c release during apoptosis, regardless of the occurrence of Bax targeting. MICS1 is cross-linked to cytochrome c without disrupting membrane integrity. Thus, MICS1 facilitates the tight association of cytochrome c with the inner membrane. Furthermore, under low-serum condition, the delay in apoptotic release of cytochrome c correlates with MICS1 up-regulation without significant changes in mitochondrial morphology, suggesting that MICS1 individually functions in mitochondrial morphology and cytochrome c release.

      DOI: 10.1091/mbc.E07-12-1205

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    • An RNAi screen for mitochondrial proteins required to maintain the morphology of the organelle in Caenorhabditis elegans 査読有り

      Ryohei Ichishita, Kousuke Tanaka, Yoshimi Sugiura, Tomoko Sayano, Katsuyoshi Mihara, Toshihiko Oka

      JOURNAL OF BIOCHEMISTRY143 ( 4 ) 449 - 454   2008年4月

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      担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

      Mitochondria are dynamic organelles that frequently divide and fuse together, resulting in the formation of intracellular tubular networks. In yeast and mammals, several factors including Drp1/Dnm1 and Mfn/Fzo1 are known to regulate mitochondrial morphology by controlling membrane fission or fusion. Here, we report the systematic screening of Caenorhabditis elegans mitochondrial proteins required to maintain the morphology of the organelle using an RNA interference feeding library. In C. elegans body wall muscle cells, mitochondria usually formed tubular structures and were severely fragmented by the mutation in fzo-1 gene, indicating that the body wall muscle cells are suitable for monitoring changes in mitochondrial morphology due to gene silencing. Of 719 genes predicted to code for most of mitochondrial proteins, knockdown of >80% of them caused abnormal mitochondrial morphology, including fragmentation and elongation. These findings indicate that most fundamental mitochondrial functions, including metabolism and oxidative phosphorylation, are necessary for maintenance of the tubular networks as well as membrane fission and fusion. This is the first evidence that known mitochondrial activities are prerequisite for regulating the morphology of the organelle. Furthermore, 88 uncharacterized or poorly characterized genes were found in the screening to be implicated in mitochondrial morphology.

      DOI: 10.1093/jb/mvm245

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    • Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission 査読有り

      Naoko Taguchi, Naotada Ishihara, Akihiro Jofuku, Toshihiko Oka, Katsuyoshi Mihara

      Journal of Biological Chemistry282 ( 15 ) 11521 - 11529   2007年4月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m607279200

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    • Identification and Characterization of a New Tom40 Isoform, a Central Component of Mitochondrial Outer Membrane Translocase 査読有り

      J.-y. Kinoshita, K. Mihara, T. Oka

      Journal of Biochemistry141 ( 6 ) 897 - 906   2007年3月27日

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      担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/jb/mvm097

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    • A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments 査読有り

      Otera H, Taira Y, Horie C, Suzuki Y, Suzuki H, Setoguchi K, Kato H, Oka T, Mihara K

      Journal of Cell Biology179 ( 7 ) 1355 - 1363   2007年

    • Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function 査読有り

      Yuka Eura, Naotada Ishihara, Toshihiko Oka, Katsuyoshi Mihara

      Journal of Cell Science119 ( 23 ) 4913 - 4925   2006年12月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:The Company of Biologists  

      Mitofusin proteins 1 and 2 (Mfn1 and Mfn2, respectively) of the mammalian mitochondrial outer membrane are homologues of Drosophila FZO and yeast Fzo1, and both are essential for GTP-dependent mitochondrial fusion. We identified a 55-kDa Mfn-binding protein named MIB. It is a member of the medium-chain dehydrogenase/reductase protein superfamily, and has a conserved coenzyme-binding domain (CBD). The majority of MIB is localized in the cytoplasm but a small amount is associated with mitochondria. Exogenous expression of MIB in HeLa cells induced mitochondrial fragmentation, which was prevented by coexpression of Mfn1, suggesting a functional interaction of MIB with Mfn proteins; the GGVG sequence in the CBD of MIB is essential for its function. By contrast, MIB knockdown resulted in growth arrest of the cells, although apoptotic sensitivity was not affected by either its knockdown or its overexpression. Furthermore, MIB knockdown induced a large extension of mitochondrial network structures. By contrast, a double knockdown of MIB and Mfn1 resulted in mitochondrial fragmentation and reversal of the growth arrest, the morphology and growth phenotype induced by knockdown of Mfn1 alone, again suggesting that MIB modulates Mfn1 function. Together, these findings suggest that MIB is essential for cellular function by regulating mitochondrial membrane dynamics in cooperation with Mfn proteins.

      DOI: 10.1242/jcs.03253

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    • IntraGolgi distribution of the Conserved Oligomeric Golgi (COG) complex 査読有り

      Eliza Vasile, Toshihiko Oka, Maria Ericsson, Nobuhiro Nakamura, Monty Krieger

      Experimental Cell Research312 ( 16 ) 3132 - 3141   2006年10月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1016/j.yexcr.2006.06.005

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    • Regulation of mitochondrial morphology through proteolytic cleavage of OPA1 査読有り

      Naotada Ishihara, Yuu Fujita, Toshihiko Oka, Katsuyoshi Mihara

      The EMBO Journal25 ( 13 ) 2966 - 2977   2006年7月12日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

      DOI: 10.1038/sj.emboj.7601184

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    • Subunit Architecture of the Conserved Oligomeric Golgi Complex 査読有り

      Daniel Ungar, Toshihiko Oka, Eliza Vasile, Monty Krieger, Frederick M. Hughson

      Journal of Biological Chemistry280 ( 38 ) 32729 - 32735   2005年9月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m504590200

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    • Genetic Analysis of the Subunit Organization and Function of the Conserved Oligomeric Golgi (COG) Complex 査読有り

      Toshihiko Oka, Eliza Vasile, Marsha Penman, Carl D. Novina, Derek M. Dykxhoorn, Daniel Ungar, Frederick M. Hughson, Monty Krieger

      Journal of Biological Chemistry280 ( 38 ) 32736 - 32745   2005年9月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m505558200

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    • The COG and COPI Complexes Interact to Control the Abundance of GEARs, a Subset of Golgi Integral Membrane Proteins 査読有り

      Toshihiko Oka, Daniel Ungar, Frederick M. Hughson, Monty Krieger

      Molecular Biology of the Cell15 ( 5 ) 2423 - 2435   2004年5月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Cell Biology (ASCB)  

      The conserved oligomeric Golgi (COG) complex is a soluble hetero-octamer associated with the cytoplasmic surface of the Golgi. Mammalian somatic cell mutants lacking the Cog1 (ldlB) or Cog2 (ldlC) subunits exhibit pleiotropic defects in Golgi-associated glycoprotein and glycolipid processing that suggest COG is involved in the localization, transport, and/or function of multiple Golgi processing proteins. We have identified a set of COG-sensitive, integral membrane Golgi proteins called GEARs (mannosidase II, GOS-28, GS15, GPP130, CASP, giantin, and golgin-84) whose abundances were reduced in the mutant cells and, in some cases, increased in COG-overexpressing cells. In the mutants, some GEARs were abnormally localized in the endoplasmic reticulum and were degraded by proteasomes. The distributions of the GEARs were altered by small interfering RNA depletion of ϵ-COP in wild-type cells under conditions in which COG-insensitive proteins were unaffected. Furthermore, synthetic phenotypes arose in mutants deficient in both ϵ-COP and either Cog1 or Cog2. COG and COPI may work in concert to ensure the proper retention or retrieval of a subset of proteins in the Golgi, and COG helps prevent the endoplasmic reticulum accumulation and degradation of some GEARs.

      DOI: 10.1091/mbc.e03-09-0699

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    • From Lysosomes to the Plasma Membrane 査読有り

      Takao Toyomura, Yoshiko Murata, Akitsugu Yamamoto, Toshihiko Oka, Ge-Hong Sun-Wada, Yoh Wada, Masamitsu Futai

      Journal of Biological Chemistry278 ( 24 ) 22023 - 22030   2003年6月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m302436200

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    • Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function 査読有り

      Daniel Ungar, Toshihiko Oka, Elizabeth E. Brittle, Eliza Vasile, Vladimir V. Lupashin, Jon E. Chatterton, John E. Heuser, Monty Krieger, M. Gerard Waters

      Journal of Cell Biology157 ( 3 ) 405 - 415   2002年4月29日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Rockefeller University Press  

      Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Three complexes that have previously been partially characterized include (a) the Golgi transport complex (GTC), identified in an in vitro membrane transport assay, (b) the ldlCp complex, identified in analyses of CHO cell mutants with defects in Golgi-associated glycosylation reactions, and (c) the mammalian Sec34 complex, identified by homology to yeast Sec34p, implicated in vesicular transport. We show that these three complexes are identical and rename them the conserved oligomeric Golgi (COG) complex. The COG complex comprises four previously characterized proteins (Cog1/ldlBp, Cog2/ldlCp, Cog3/Sec34, and Cog5/GTC-90), three homologues of yeast Sec34/35 complex subunits (Cog4, -6, and -8), and a previously unidentified Golgi-associated protein (Cog7). EM of ldlB and ldlC mutants established that COG is required for normal Golgi morphology. “Deep etch” EM of purified COG revealed an ∼37-nm-long structure comprised of two similarly sized globular domains connected by smaller extensions. Consideration of biochemical and genetic data for mammalian COG and its yeast homologue suggests a model for the subunit distribution within this complex, which plays critical roles in Golgi structure and function.

      DOI: 10.1083/jcb.200202016

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    • a4, a Unique Kidney-specific Isoform of Mouse Vacuolar H+-ATPase Subunit a 査読有り

      Toshihiko Oka, Yoshiko Murata, Miwako Namba, Takao Yoshimizu, Takao Toyomura, Akitsugu Yamamoto, Ge-Hong Sun-Wada, Naotaka Hamasaki, Yoh Wada, Masamitsu Futai

      Journal of Biological Chemistry276 ( 43 ) 40050 - 40054   2001年10月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m106488200

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    • Four Subunit a Isoforms ofCaenorhabditis elegans Vacuolar H+-ATPase 査読有り

      Toshihiko Oka, Takao Toyomura, Kenta Honjo, Yoh Wada, Masamitsu Futai

      Journal of Biological Chemistry276 ( 35 ) 33079 - 33085   2001年8月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m101652200

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    • Requirement of V-ATPase for Ovulation and Embryogenesis inCaenorhabditis elegans 査読有り

      Toshihiko Oka, Masamitsu Futai

      Journal of Biological Chemistry275 ( 38 ) 29556 - 29561   2000年9月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.m002756200

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    • Upstream Regions Directing Heart-Specific Expression of the GATA6 Gene During Mouse Early Development 査読有り

      G.-H. Sun-Wada, S. Manabe, T. Yoshimizu, C. Yamaguchi, T. Oka, Y. Wada, M. Futai

      Journal of Biochemistry127 ( 4 ) 703 - 709   2000年4月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a022660

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    • Three Subunit a Isoforms of Mouse Vacuolar H+-ATPase 査読有り

      Takao Toyomura, Toshihiko Oka, Chie Yamaguchi, Yoh Wada, Masamitsu Futai

      Journal of Biological Chemistry275 ( 12 ) 8760 - 8765   2000年3月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.275.12.8760

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    • Disruption of clh-1, a chloride channel gene, results in a wider body of Caenorhabditis elegans 査読有り

      Mark I.R Petalcorin, Toshihiko Oka, Makoto Koga, Ken-ichi Ogura, Yoh Wada, Yasumi Ohshima, Masamitsu Futai

      Journal of Molecular Biology294 ( 2 ) 347 - 355   1999年11月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1006/jmbi.1999.3241

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    • A pair of invertedly repeated genes in Chlamydomonas reinhardtii encodes a zygote-specific protein whose expression is UV-sensitive 査読有り

      Hidenobu Uchida, Lena Suzuki, Toyoaki Anai, Koji Doi, Hiroyoshi Takano, Hirofumi Yamashita, Toshihiko Oka, Shigeyuki Kawano, Ken-Ichi Tomizawa, Tamotsu Kawazu, Haruko Kuroiwa, Tsuneyoshi Kuroiwa

      Current Genetics36 ( 4 ) 232 - 240   1999年10月13日

      詳細を見る

      掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

      DOI: 10.1007/s002940050495

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      その他リンク: http://link.springer.com/article/10.1007/s002940050495/fulltext.html

    • Identification of SEC12, SED4, Truncated SEC16, and EKS1/HRD3 as Multicopy Suppressors of ts Mutants of Sari GTPase 査読有り

      Y. Saito, T. Yamanushi, T. Oka, A. Nakano

      Journal of Biochemistry125 ( 1 ) 130 - 137   1999年1月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a022249

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    • Identification and Cloning of Rat Galectin-2: Expression Is Predominantly in Epithelial Cells of the Stomach 査読有り

      Toshihiko Oka, Seiko Murakami, Yoichiro Arata, Jun Hirabayashi, Ken-Ichi Kasai, Yoh Wada, Masamitsu Futai

      Archives of Biochemistry and Biophysics361 ( 2 ) 195 - 201   1999年1月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1006/abbi.1998.0968

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    • Identification of the copper chaperone, CUC-1, in<i>Caenorhabditis elegans</i>: tissue specific co-expression with the copper transporting ATPase, CUA-1 査読有り

      Tokumitsu Wakabayashi, Norihiro Nakamura, Yoshihiro Sambongi, Yoh Wada, Toshihiko Oka, Masamitsu Futai

      FEBS Letters440 ( 1-2 ) 141 - 146   1998年11月27日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

      DOI: 10.1016/s0014-5793(98)01431-8

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    • Activities of Mutant Sar1 Proteins in Guanine Nucleotide Binding, GTP Hydrolysis, and Cell-Free Transport from the Endoplasmic Reticulum to the Golgi Apparatus 査読有り

      Y. Saito, K. Kimura, T. Oka, A. Nakano

      Journal of Biochemistry124 ( 4 ) 816 - 823   1998年10月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a022185

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    • Multiple Genes for Vacuolar-type ATPase Proteolipids inCaenorhabditis elegans 査読有り

      Toshihiko Oka, Ryuji Yamamoto, Masamitsu Futai

      Journal of Biological Chemistry273 ( 35 ) 22570 - 22576   1998年8月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.273.35.22570

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    • Three vha Genes Encode Proteolipids ofCaenorhabditis elegans Vacuolar-type ATPase 査読有り

      Toshihiko Oka, Ryuji Yamamoto, Masamitsu Futai

      Journal of Biological Chemistry272 ( 39 ) 24387 - 24392   1997年9月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1074/jbc.272.39.24387

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    • Caenorhabditis elegans cDNA for a Menkes/Wilson Disease Gene Homologue and Its Function in a Yeast CCC2 Gene Deletion Mutant 査読有り

      Y. Sambongi, T. Wakabayashi, T. Yoshimizu, H. Omote, T. Oka, M. Futai

      Journal of Biochemistry121 ( 6 ) 1169 - 1175   1997年6月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a021711

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    • Characterization of Yeast sar1 Temperature-Sensitive Mutants, Which Are Defective in Protein Transport from the Endoplasmic Reticulum 査読有り

      T. Yamanush, A. Hirata, T. Oka, A. Nakano

      Journal of Biochemistry120 ( 2 ) 452 - 458   1996年8月1日

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a021432

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    • The Rat Intrinsic Factor Gene: Its 5′-Upstream Region and Chief Cell-Specific Transcription1 査読有り

      Masatomo Maeda, Seikyo Asahara, Tsuyoshi Nishi, Sotaro Mushiake, Toshihiko Oka, Shoichi Shimada, Tsutomu Chiba, Masaya Tohyama, Masamitsu Futai

      The Journal of Biochemistry117 ( 6 ) 1305 - 1311   1995年6月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a124859

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    • Identification of the Promoter Region of the Human Histamine H2-Receptor Gene 査読有り

      T. Nishi, T. Koike, T. Oka, M. Maeda, M. Futai

      Biochemical and Biophysical Research Communications210 ( 2 ) 616 - 623   1995年5月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

      DOI: 10.1006/bbrc.1995.1703

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    • Mutational Analysis of the Sar1 Protein, a Small GTPase Which Is Essential for Vesicular Transport from the Endoplasmic Reticulum1 査読有り

      Akihiko Nakano, Hideshi Otsuka, Mami Yamagishi, Eiichi Yamamoto, Keitaro Kimura, Shuh-ichi Nishikawa, Toshihiko Oka

      The Journal of Biochemistry116 ( 2 ) 243 - 247   1994年8月

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      掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a124513

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    • Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast 査読有り

      Toshihiko Oka, Akihiko Nakano

      Journal of Cell Biology124 ( 4 ) 425 - 434   1994年

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      記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Rockefeller University Press  

      The SAR1 gene product (Sar1p), a 21-kD GTPase, is a key component of the ER-to-Golgi transport in the budding yeast. We previously reported that the in vitro reconstitution of protein transport from the ER to the Golgi was dependent on Sar1p and Sec12p (Oka, T., S. Nishikawa, and A. Nakano. 1991. J. Cell Biol. 114:671-679). Sec12p is an integral membrane protein in the ER and is essential for the Sar1 function. In this paper, we show that Sar1p can remedy the temperature-sensitive defect of the sec12 mutant membranes, which is in the formation of ER-to-Golgi transport vesicles. The addition of Sar1p promotes vesicle formation from the ER irrespective of the GTP- or GTPγS- bound form, indicating that the active form of Sar1p but not the hydrolysis of GTP is required for this process. The inhibition of GTP hydrolysis blocks transport of vesicles to the Golgi and thus causes their accumulation. The accumulating vesicles, which carry Sar1p on them, can be separated from other membranes, and, after an appropriate wash that removes Sar1p, are capable of delivering the content to the Golgi when added back to fresh membranes. Thus we have established a new method for isolation of functional intermediate vesicles in the ER-to-Golgi transport. The sec23 mutant is defective in activation of Sar1 GTPase (Yoshihisa, T., C. Barlowe, and R. Schekman. 1993. Science (Wash. DC). 259:1466-1468). The membranes and cytosol from the sec23 mutant show only a partial defect in vesicle formation and this defect is also suppressed by the increase of Sar1p. Again GTP hydrolysis is not needed for the suppression of the defect in vesicle formation. Based on these results, we propose a model in which Sar1p in the GTP-bound form is required for the formation of transport vesicles from the ER and the GTP hydrolysis by Sar1p is essential for entering the next step of vesicular transport to the Golgi apparatus.

      DOI: 10.1083/jcb.124.4.425

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    • Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. 査読有り

      Toshihiko Oka, Shuh-ichi Nishikawa, Akihiko Nakano

      Journal of Cell Biology114 ( 4 ) 671 - 679   1991年8月15日

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      担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Rockefeller University Press  

      In the yeast secretory pathway, two genes SEC12 and SAR1, which encode a 70-kD integral membrane protein and a 21-kD GTP-binding protein, respectively, cooperate in protein transport from the ER to the Golgi apparatus. In vivo, the elevation of the SAR1 dosage suppresses temperature sensitivity of the sec12 mutant. In this paper, we show cell-free reconstitution of the ER-to-Golgi transport that depends on both of these gene products. First, the membranes from the sec12 mutant cells reproduce temperature sensitivity in the in vitro ER-to-Golgi transport reaction. Furthermore, the addition of the Sar1 protein completely suppresses this temperature-sensitive defect of the sec12 membranes. The analysis of Sar1p partially purified by E. coli expression suggests that GTP hydrolysis is essential for Sar1p to execute its function.

      DOI: 10.1083/jcb.114.4.671

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    ▼全件表示

    MISC

    • PKAはMIC60のリン酸化を介してPINK1とParkinによるミトコンドリア品質管理を制御する 招待有り

      赤羽しおり, 岡 敏彦

      実験医学   2016年

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      記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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    • ミトコンドリア形態異常と疾患 招待有り

      岡 敏彦

      医学のあゆみ   2015年

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      記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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    • Regulation and Physiologic Functions of GTPases in Mitochondrial Fusion and Fission in Mammals 招待有り

      Naotada Ishihara, Hidenori Otera, Toshihiko Oka, Katsuyoshi Mihara

      ANTIOXIDANTS & REDOX SIGNALING19 ( 4 ) 389 - 399   2013年8月

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      記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MARY ANN LIEBERT, INC  

      Significance: Mitochondria are double membrane-bound organelles with tubular network structures that are essential for oxidative ATP production and play pivotal roles in regulating calcium homeostasis and apoptosis. Furthermore, mitochondria produce large amounts of reactive oxygen species that are fatal to cellular functions through uncoupled respiration. These organelles dynamically change their morphology by frequent fusion and fission, and three types of high molecular weight GTPase proteins have been identified as core components of the fusion and fission machineries. Recent Advances: Here, we review recent advances in the study of mitochondrial fission and fusion GTPases and their physiologic roles in mammalian cells. The regulation of mitochondrial dynamics coupled with a quality control system is essential for cellular homeostasis, development, and tissue differentiation. Defects of these mechanisms cause various disorders, including neurodegenerative diseases, such as Parkinson's disease, Huntington's disease, and Alzheimer's disease. Critical Issues: Although a significant amount of relevant data has accumulated on the regulation of mammalian mitochondrial fusion and fission, mechanistic molecular details and cellular functions still remain insufficiently defined. Future Directions: Elucidating the physiologic roles of mitochondrial fusion and fission in highly differentiated cells using tissue-specific knockout mice remains a challenge for the future.

      DOI: 10.1089/ars.2012.4830

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    • ミトコンドリア膜構造変化とアポトーシス制御 招待有り

      大寺秀典, 岡 敏彦

      細胞工学   2010年

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      記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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    • Retrograde transport on the COG railway 招待有り

      D Ungar, T Oka, M Krieger, FM Hughson

      TRENDS IN CELL BIOLOGY16 ( 2 ) 113 - 120   2006年2月

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      記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE LONDON  

      The conserved oligomeric Golgi (COG) complex is essential for establishing and/or maintaining the structure and function of the Golgi apparatus. The Golgi apparatus, in turn, has a central role in protein sorting and glycosylation within the eukaryotic secretory pathway. As a consequence, COG mutations can give rise to human genetic diseases known as congenital disorders of glycosylation. We review recent results from studies of yeast, worm, fly and mammalian COG that provide evidence that COG might function in retrograde vesicular trafficking within the Golgi apparatus. This hypothesis explains the impact of COG mutations by postulating that they impair the retrograde flow of resident Golgi proteins needed to maintain normal Golgi structure and function.

      DOI: 10.1016/j.tcb.2005.12.004

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    • A railroad switch in mitochondrial protein import 招待有り

      T Oka, K Mihara

      MOLECULAR CELL18 ( 2 ) 145 - 146   2005年4月

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      記述言語:英語   掲載種別:その他   出版者・発行元:CELL PRESS  

      Chacinska et al. (2005) recently clarified how translocation machineries of the mitochondrial outer and inner membranes cooperate to correctly sort preproteins destined for the mitochondrial matrix and inner membrane.

      DOI: 10.1016/j.molcel.2005.03.022

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    • Multi-component protein complexes and Golgi membrane trafficking 招待有り

      T Oka, M Krieger

      JOURNAL OF BIOCHEMISTRY137 ( 2 ) 109 - 114   2005年2月

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      記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

      Several large cytosolic protein complexes with multiple components have been proposed to play key roles in mediating or controlling membrane trafficking. Among these complexes, TRAPP, COG and GARP/VFT have been implicated in multiple steps of Golgi membrane trafficking. The importance of these complexes for Golgi function has been established using in vitro biochemical assays and yeast and mammalian somatic cell genetics. Furthermore, mutations in the genes encoding subunits of either TRAPP or the COG complex have been shown to be responsible for human genetic disorders. We here review recent studies exploring the structures and functions of these three oligomeric complexes.

      DOI: 10.1093/jb/mvi024

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    • Oligosaccharide specificity of galectins: a search by frontal affinity chromatography

      Jun Hirabayashi, Tomomi Hashidate, Yoichiro Arata, Nozomu Nishi, Takanori Nakamura, Mitsuomi Hirashima, Tadasu Urashima, Toshihiko Oka, Masamitsu Futai, Werner E.G Muller, Fumio Yagi, Ken-ichi Kasai

      Biochimica et Biophysica Acta (BBA) - General Subjects1572 ( 2-3 ) 232 - 254   2002年9月

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      出版者・発行元:Elsevier BV  

      DOI: 10.1016/s0304-4165(02)00311-2

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    • Luminal acidification of diverse organelles by V-ATPase in animal cells

      M. Futai, T. Oka, G. Sun-Wada, Y. Moriyama, H. Kanazawa, Y. Wada

      Journal of Experimental Biology203 ( 1 ) 107 - 116   2000年1月1日

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      出版者・発行元:The Company of Biologists  

      Eukaryotic cells contain organelles bounded by a single membrane in the cytoplasm. These organelles have differentiated to carry out various functions in the pathways of endocytosis and exocytosis. Their lumina are acidic, with pH ranging from 4.5 to 6.5. This article describes recent studies on these animal cell organelles focusing on (1) the primary proton pump (vacuolar-type H(+)-ATPase) and (2) the functions of the organelle luminal acidity. We also discuss similarities and differences between vacuolar-type H(+)-ATPase and F-type ATPase. Our own studies and interests are emphasized.

      DOI: 10.1242/jeb.203.1.107

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    • Diverse Roles of Single Membrane Organelles: Factors Establishing the Acid Lumenal pH

      M. Futai, T. Oka, Y. Moriyama, Y. Wada

      Journal of Biochemistry124 ( 2 ) 259 - 267   1998年8月1日

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      出版者・発行元:Oxford University Press (OUP)  

      DOI: 10.1093/oxfordjournals.jbchem.a022105

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    • Purification and assay of yeast Sarlp

      Keitarou Kimura, Toshihiko Oka, Akihiko Nakano

      Small GTPases and Their Regulators Part C: Proteins Involved in Transport   41 - 49   1995年

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      出版者・発行元:Elsevier  

      DOI: 10.1016/s0076-6879(95)57008-x

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    • 酵母における小胞体-ゴルジ体間の小胞輸送

      岡 敏彦, 中野明彦

      新生化学実験講座第6巻生体膜と膜輸送下   615 - 623   1992年

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