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The Mechanism of Protein Targeting to and Translocation across The Mitochondrial Outermembrane

Research Project

Project/Area Number 09308022
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

MIHARA Katsuyoshi  Graduate School of Medical Science, Kyushu University, Professor, 大学院・医学系研究科, 教授 (40029963)

Co-Investigator(Kenkyū-buntansha) KOMIYA Tohru  Graduate School of Medical Science, Kyushu University, Research Associate, 大学院・医学系研究科, 助手 (40304802)
SAKAGUCHI Masao  Graduate School of Medical Science, Kyushu University,Associate Professor, 大学院・医学系研究科, 助教授 (30205736)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥31,900,000 (Direct Cost: ¥31,900,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1998: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥17,100,000 (Direct Cost: ¥17,100,000)
Keywordsmitochondria / protein import / membrane translation / precursor proteins / chaperones / 全駆体蛋白質 / シグナルペプチド / TOM / TIM
Research Abstract

Research efforts have been dealt with the following aspects.
(1) Analysis of the function of cytoplasmic chaperones, MSF (mitochondrial import stimulation factor) and hsp70 in preprotein targeting to mitochondria ; we have shown that correct targeting of precursor proteins to mitochondrial import receptors is determined by cytoplasmic chaperones, irrespective of the presence or absence of a cleavable presequence.
(2) The mechanism of preprotein translocation across the mitochondrial outer membrane ; we have shown that specific and sequential binding of a targeting signal to strategically situated acidic receptors delivers a precursor across the outer mitochondrial membrane.
(3) Characterization of preprotein import factors of mammalian mitochondria ; we have identified and cloned tow novel import factors, metaxin and OM37, when seemed to function as the import receptors of mammalian mitochondria.
(4) The mechanism of mitochondria targeting of mitochondrail outer membrane proteins ; we have shown that the N-terminal transmembrane segment with appropriate hydrophobicity cooperates with a net positive charge in the flanking segment to function as the mitochondria targeting signal.
(5) The mechanism of cytochrome c export from mitochondria in response to apoptotic signals ; we have reconstituted the cytochome c export reaction using isolated mitochondria, cytosol, dATP (or ATP) and staurosporine. This system enabled purification of the export stimulation factor from the cytosol.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Y. Abe: "Sturctural basis of presequence recognition by the mitochondrial protein import receptor Tom20."Cell. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Mihara: "Targeting and insertion of nuclear-encoded preproteins into the mitochondrial outer membrane."BioEssays. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Nakai: "Membrane topology of Alzheimer's disease-related Presenilin1 -Evidence for the existence of a molecular species with a seven membrane-spanning and one membrane-embedded structure"J. Biol. Chen. 274. 23647-23658 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Sakaki: "Membrane perturbing factor in reticulocyte lystae, which is transiently activated by proteses."FEBS Letters. 454. 345-348 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Ota: "Assessment of topogenic functions of anticipated transmembrane segments of human Band3."J. Biol. Chem.. 273. 28286-28291 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Ishihara: "Characterization of the initial steps of preprotein import into rat liver mitoplasts."J. Biochem.. 124. 824-834 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Nakamura: "Identification of a novel anterograde transport signal on Emp24p."Mol. Biol. Cell. 9. 3493-3503 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Ota: "Forced tranamembrane orientation of hydrophilic polypeptide segments in multispanning membrane proteins"Molecular Cell. 2. 495-503 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Komiya: "Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: Evidence for the "acid chain" hypothesis."EMBOJ.. 17. 3886-3898 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Kida: "Membrane topology of NADPH-cytochrome P450 reductase on the endoplasmic reticulum."Arch. Biochem. Biophys.. 351. 175-179 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Ishihara: "Identification of the protein import components of the rat mitochondrial inner membrane, Rtim17, Rtim23 and Rtim44."J. Biochem.. 123. 722-732 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Iwahashi: "Analysis of the functional domain of the rat liver mitochondrial import receptor Tom20."J. Biol. Chem.. 272. 18467-18472 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Abe, T.Shoda, T.Muto, K.Mihara, H.Torii, S.Nishikawa, T.Endo & D.Kohda: "Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20"Cell. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Ota, M.Sakaguchi, N.Hamasaki & K.Mihara: "Assessment of topogenic functions of anticipated transmembrane segments of human Band3"J.Biol. Chem.. 272. 28286-28291 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Mihara: "Targeting and insertion of nuclear-encoded preproteins into the mitochondrial outer membrane"BioEssays.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Ishihara, K.Tomiya, M.Sakaguchi, A.Ito & K.Mihara: "Characterization of the initial steps of preprotein import into rat liver mitoplasts"J.Biochem.. 124. 824-834 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Nakai, A.Yamasaki, M.Sakaguchi, K.Kosaka, K.Mihara, Y.Amaya & S.Miura: "Membrane topology of Alzheimer's disease-related Presenilin 1 - Evidence for the existence of a molecular species with a seven membrane - spanning and one membrane-embedded structure"J. Biol. Chem.. 274. 23647-23658 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Nakamura, S.Yamazaki, K.Sato, A.Nakano, M.Sakaguchi & K.Mihara: "Identification of potential regulatory elements for the transport of Emp24p"Mol. Biol. Cell. 9. 3493-3503 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Sakaki, M.Sakaguchi, K.Ota & K.Mihara: "Membrane perturbing factor in reticulocyte lysate, which is transiently activated proteases"FEBS Letters. 454. 345-348 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Ota, M.Sakaguchi, G.von Heijne, N.Hakasaki & K. Mihara: "Forced transmembrane orientation of hydrophilic polypeptide segments in multispanning membrane proteins"Mol. Cell. 2. 495-503 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Komiya, S.Rospert, C.Koehler, R.Looser, G.Schatz & K.Mihara: "Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway : Evidence for the "acid chain hypothesis""EMBO J.. 17. 3886-3898 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J.Iwahashi, S.Yamazaki, T.Komiya, N.Nomura, S.Nishikawa, T.Endo & K.Mihara: "Analysis of the functional domain of the rat liver mitochondrial import receptor Tom20"J.Boil. Chem.. 272. 18467-18472 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Ishhara & K.Mihara: "Identification of the protein import component of the rat mitochondrial inner membrane, rTIM17, rTIM23 and rTIM44"J. Biochem.. 123. 722-732 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Kida, S.Ohgiya, K.Mihara & M.Sakaguchi: "Membrane topology of NADPH-cytochrome P450 reductase on the endoplasmic reticulum"Arch. Biochem. Biophys.. 351. 175-179 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Komiya, S.Rospert, G.Schatz & K.Mihara: "Binding of mitochondrial precursor proteins to the cytoplasmic domains of the import receptors Tom70 and Tom20 is determined by cytoplasmic chaperones"EMBO J.. 16. 4267-4275 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] L.C. Armstrong, T.Komiya, B.E.Bergman, K.Mihara & P.Bornstein: "Metaxin is a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion"J.Biol. Chem.. 272. 6510-6518 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Abe: "Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20."Cell. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Mihara: "Targeting and insertionof nuclear-encoded preproteins into the mitochondrial outer membrane."BioEssays. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Nakai: "Membrane topology of Alzheime's disease-related Presenilinl-Evidence for the existence of a molecular species with a seven membrane-spanning and on membrane-embedded structure."J.Biol,Chem,. 274. 23647-23658 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Sakaki: "Membrane perturbing factor in reticulocyte lysate,wich is transiently activated by proteases."FEBS Leetter. 454. 345-348 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ota: "Assessment of topogenic functons of anticipated transmembrane segments of human Band3." J.Biol.Chem.273. 28286-28291 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.NIshihara: "Characterization of the initial steps of preprotein import into rat liver mitoplasts." J.Biochem.124. 824-834 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Nakamura: "Identification of a novel anterograde transport s ignal on Emp24p." Mol.Biol.Cell. 9. 3493-3503 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Oda: "Forced transmembrane orientation of hydrophilic polypeptide seg-ments in multispanning membrane proteins." Molecular Cell. 2. 495-503 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Komiya: "Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway:Evidence for the “acid chain"hypothesis." EMBO J.17. 3886-3898 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Kida: "Membrane toplogy of NADPH-cytochrome P450 reductase on the endo-plasmic reticulum." Arch.Biochem.Biophys.351. 175-179 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Ishihara: "Identification of the protein import components of the rat mito-chondrial inner menbrane,rTIM17,rTIM23 and rTIM44." J.Biochem.123. 722-732 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Iwahashi: "Analysis of the functional domain of the rat liver mitochondrial import receptor Tom20." J.Biol.Chem.272. 18467-18472 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Komiya: "Binding of mitochondrial precursor proteins to the cytoplasmic domains of the import receptors Tom70 and Tom20 is determined by cytoplasmic chaperones." EMBOJ.16. 4267-4275 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] L.C.Armstrong: "Metaxin is a component of a preprotein import complex in the outer membrane of the mammalian mitochondria." J.Biol.Chem.272. 6510-6518 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Ishihara: "Identification of the protein import components of the rat mitochon-drial inner membrane,rTIM17,rTIM23 and rTIM44." J.Biochem.(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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