• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2006 Fiscal Year Final Research Report Summary

Molecular mechanisms of mitochondrial biogenesis and morphology regulation

Research Project

Project/Area Number 14002007
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

MIHARA Katsuyoshi  Kyushu University, Graduate School of Medical Science, Research Professor (40029963)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Naotada  Tokyo Medical and Dental University, Graduate School and Faculty of Medicine, Research Associate (10325516)
KOMIYA Tohru  Nagahama Institute of Bio-Science and Technology, Department of Bio-Science, Associate Professor (40304802)
Project Period (FY) 2002 – 2006
Keywordsmitochondria / membrane protein topogcnesis / membrane translocation / membrane fusion / membrane division / precursor protein / membrane protein / signal recognition
Research Abstract

Mitochondria are involved in several fundamental cellular processes in higher eukaryotes including oxidative phosphorylation, calcium-signaling, and apoptosis. They are extremely dynamic entities changing their size, shape, position or copy number in cells during cellular differentiation, development, or under pathologic conditions. The majority of mitochondrial proteins are encoded by nuclear DNA, synthesized in the cytosol, and imported post-translationally into the mitochondrial sub-compartments. We have made the following progress toward the aim of two sub-projects, which contributed much in understanding the mechanisms of mammalian mitochondrial biogenesis and morphology regulation on the molecular level.
Targeting and topogenesis of mitochondrial membrane proteins: We analyzed targeting and insertion pathway of mitochondrial membrane proteins with distinct localization and topology including the N-terminal signal anchored proteins and. Most importantly, these experiments revealed … More that (1) C-terminal tail-anchored proteins of the outer membrane are integrated into the membrane through a common pathway independent of the TOM components, and that (ii) mitochondrial outer membrane proteins with multiple transmembrane segments are integrated into the membrane through a novel pathway that requires both Tom70 and intermembrane space components, but not the other TOM components. Furthermore, we characterized Tom40 as a preprotein translocating channel, and newly identified the import components of mammalian mitochondria, Tom70, Tom5, Tom6 and Tom40b.
Regulation of mitochondrial morphology and apoptosis: Although mitochondrial dynamic morphological changes are considered crucial for cellular functions, the underlying mechanisms, mainly in mammals, are poorly understood. We are devoting our efforts to studies of three mammalian GTP-binding proteins that are implicated in mitochondrial membrane morphogenesis and obtained the following results. (i) Identification of two mammalian mitochodnrial outrmembrane GTPases, Mfn1 and Mfn2, essential for fusion reaction; (ii) Identification of a novel protein MIB that negatively regulates activity of Mfn proteins; (iii) First demonstration of the importance of processing of the innermembrane GTPase OPA1 for mitochondrial fusion, and identification of the processing enzyme; (iv) Analysis of the function of cytoplasmic GTPase Drpl during cell cycle progression; (v) Production of DRP1-knockout mice; (vi) Demonstration of the importance of processing for the release Apoptosis Inducing Factor (AIF) from the intermembrane space; (vii) Identification of mitochondrial inner membrane protein MICS1 required for mitochondrial cristae and structure regulation; and (viii) Demonstration of the importance of the inner membrane Leucine zipper-, EF-hand-containing protein LETM1 for maintenance of the respiratory complexes and inner membrane structure. Less

  • Research Products

    (36 results)

All 2008 2007 2006 2005 2004 2003 2002

All Journal Article (36 results)

  • [Journal Article] An RNAi screen for mitochondrial proteins required to maintain the morphology of the organelle in C. elegans2008

    • Author(s)
      R. Ichishita, et al.
    • Journal Title

      J. Biohcem. 143(in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An RNAi screen for mitochondrial proteins required to maintain the morphology of the organelle in C. elegans2008

    • Author(s)
      R. Ichishita, et al.
    • Journal Title

      J. Biochem. 143(in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tom22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax2007

    • Author(s)
      G. Bellot, et al.
    • Journal Title

      Cell Death and Differentiation 14

      Pages: 785-794

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission2007

    • Author(s)
      N. Tagudhi, et al.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 11521-11529

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification and characterization of a new Tom40 isoform, a central component of mitochondrial outer membrane translocase2007

    • Author(s)
      J. Kinoshita, et al.
    • Journal Title

      J. Biochem. 141

      Pages: 897-906

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments2007

    • Author(s)
      H. Otera, et al.
    • Journal Title

      J. Cell Biol. 179

      Pages: 1355-1363

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission2007

    • Author(s)
      N. Taguchi, et al.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 11521-11529

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Function of positive charges following signal-anchor sequences during translocation of the N-terminal domain2006

    • Author(s)
      Y. Kida, et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 1152-1158

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ubiquitin-proteasome-dependent degradation of mammalian ER stearoyl-CoA desaturase2006

    • Author(s)
      H. Kato, et al.
    • Journal Title

      J. Cell Sci. 119

      Pages: 2342-2353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of mitochondrial morphology through proteolytic cleavage of OPA12006

    • Author(s)
      N. Ishihara, et al.
    • Journal Title

      EMBO J. 25

      Pages: 2966-2977

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function2006

    • Author(s)
      Y. Eura, et al.
    • Journal Title

      J. Cell Sci. 119

      Pages: 4913-4925

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteins2006

    • Author(s)
      K. Setoguchi, et al.
    • Journal Title

      EMBO J. 25

      Pages: 5635-5647

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space2005

    • Author(s)
      H. Otera, et al.
    • Journal Title

      EMBO J. 24

      Pages: 1375-1386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Switching the sorting mode of membrane proteins from cotranslational endoplasmic reticulum targeting to posttranslational mitochondrial import2005

    • Author(s)
      E. Miyazaki, et al.
    • Journal Title

      Mol. Biol. Cell 16

      Pages: 1788-1799

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analysis of functional domains of rat mitochondrial Fisl, the mitochondrial fission-stimulating protein2005

    • Author(s)
      A. Jofuku, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 333

      Pages: 650-659

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Translocation of a long amino-terminal domain through ER membrane by following signal-anchor sequence2005

    • Author(s)
      Y. Kida, et al.
    • Journal Title

      EMBO J. 24

      Pages: 3202-3213

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Switching the sorting mode of membrane proteins from cotranslationalendoplasmic reticulum targeting to posttranslational mitochondrial import2005

    • Author(s)
      E. Miyazaki, et al.
    • Journal Title

      Mol. Biol. Cell 16

      Pages: 1788-1799

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of functional domains of rat mitochondrial Fis1, the mitochondrial fission-stimulating protein2005

    • Author(s)
      A. Jofuku, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 333

      Pages: 650-659

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Targeting and assembly of rat mitochondrial translocase of outer membrane22 (TOM22) into the TOM complex2004

    • Author(s)
      Y. Nakamura, et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 21223-21232

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells2004

    • Author(s)
      Y. Zhu, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. 101

      Pages: 7681-7686

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Membrane-embedded C-terminal segment of rat mitochondrial TOM40 constitutes protein-conducting pore with enriched β-structure2004

    • Author(s)
      H. Suzuki, et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 50619-50629

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity2004

    • Author(s)
      N. Ishihara, et al.
    • Journal Title

      J. Cell Sci. 117

      Pages: 6535-6546

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Topogenesis of NHE1 : direct insertion of the membrane loop and sequestration of cryptic glycosylation and processing sites just after TM92004

    • Author(s)
      Y. Sato, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 324

      Pages: 281-287

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Membrane-embedded C-terminal segment of rat mitochondrial TOM40 constitutes protein-conducting pore with enriched β -structure2004

    • Author(s)
      H. Suzuki, et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 50619-50629

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells2003

    • Author(s)
      N. Ishihara, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 301

      Pages: 891-898

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Moving inside membranes2003

    • Author(s)
      K. Mihara
    • Journal Title

      Nature 424

      Pages: 505-506

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Two Mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion2003

    • Author(s)
      Y. Eura, et al.
    • Journal Title

      J. Biochem. 134

      Pages: 333-344

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Response of genes associated with mitochondrial function to mild heat stress in yeast Saccharomyces cerevisiae2003

    • Author(s)
      K. Sakaki, et al.
    • Journal Title

      J. Biohem. 134

      Pages: 373-384

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Targeting and assembly of mitochondrial tail-anchored proteinTom5 to the TOM complex depend on a signal distinct from that of tail-anchored proteins dispersed in the membrane2003

    • Author(s)
      C. Horie, et al.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 41462-41471

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Response of genes associated with mitochondrial function to mildheat stress in yeast Saccharomyces cerevisiae2003

    • Author(s)
      K. Sakaki, et al.
    • Journal Title

      J. Biochem. 134

      Pages: 373-384

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Targeting and assembly of mitochondrial tail-anchored protein Tom5 to the TOM complex depend on a signal distinct from that of tail-anchored proteins dispersed in the membrane2003

    • Author(s)
      C. Horie, et al.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 41462-41471

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of signal that directs C-tail-anchored proteins to mammalian mitochondrial outer membrane2002

    • Author(s)
      C. Horie, et al.
    • Journal Title

      Mol. Biol. Cell 13

      Pages: 1615-1625

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of rat TOM70 as a receptor of the preprotein translocase of the mitochondrial outer membrane2002

    • Author(s)
      H. Suzuki, et al.
    • Journal Title

      J. Cell Sci. 115

      Pages: 1895-1905

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Membrane topogenesis of the three amino-terminal transmembrane segments of glucose-6-phosphatase on endoplasmic reticulum2002

    • Author(s)
      K. Ukaji, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 292

      Pages: 153-160

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mammalian mitochondrial endonuclease G : Digestion of R-loops and localization in intermembrane space2002

    • Author(s)
      T. Ohsato, et al.
    • Journal Title

      Eur. J. Biochem. 269

      Pages: 5765-5770

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The tenth membrane region of band3 is initially exposed to the luminal side of the endoplasmic reticulum and then integrated into a partially folded band 3 intermediate2002

    • Author(s)
      T. Kanki, et al.
    • Journal Title

      Biochemistry 41

      Pages: 13973-13981

    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2010-06-09  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi