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Molecular Anatomy of Peroxisome Biogenesis and Human Disorders

Research Project

Project/Area Number 15207014
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

FUJIKI Yukio  Kyushu University, Faculty of Sciences, Professor, 大学院理学研究院, 教授 (70261237)

Co-Investigator(Kenkyū-buntansha) TAMURA Shigehiko  Kyusyu University, Faculty of Sciences, Associate Professor, 大学院理学研究院, 助教授 (90236753)
HARANO Tomoyuki  Kyushu University, Faculty of Sciences, Assistant Professor, 大学院理学研究院, 助手 (80037275)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000)
Fiscal Year 2006: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2005: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2004: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2003: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywordsperoxisome / CHO mutant cell / peroxisome biogenesis disorders / membrane biogenesis / PEX gene / peroxin / ペルオキシソーム形成因子 / タンパク質膜透過機構 / 膜透過装置 / 病因遺伝子 / AAAファミリー / ペルオキシソームの増殖・分裂 / 膜タンパク質
Research Abstract

Peroxisomal proteins, including membrane proteins, are encoded by nuclear genes and translated on free polyribosomes in the cytosol. The functional consequence of human peroxisomes is highlighted by fatal genetic peroxisome biogenesis disorders (PBD), including Zellweger syndrome, all of which are linked to a failure of peroxisome assembly. The successful isolation of animal cell mutants prompted us to search for the genes essential for peroxisome assembly. We earlier cloned nine peroxin cDNAs, including PEX1,PEX2 (formerly PAF-1), PEX3,PEX5,PEX6,PEX12,PEX13,PEX14,and PEX19,by functional phenotype- complementation assay on CHO cell mutants; PEX10 and PEX16 by the expressed sequence tag search using yeast genes. We and other groups showed these PEXs to be responsible for human PBD.
During the investigation supported by this Grant-in-Aid, we finally succeeded in cloning of a complementing cDNA, PEX26, for a CHO cell mutant ZP167 of the complementation group 8 (CG8,CG-A in Japan). Pex26p, a type-II peroxisomal membrane protein, recruits Pexlp-Pex6p complexes to peroxisomes. We also showed PEX26 is indeed responsible for PBD of CG8. By cloning of PEX26,the mission of search for pathogenic genes for all PBDs has been accomplished. Meanwhile, we recently demonstrated that a mobile shuttling peroxisome targeting signal 1(PTS1)-receptor, Pex5p, carrying the cargos docks with the initial site Pexl4p in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, Pex10p, and Pex12p, using CHO cell mutants, pex2, pex12, pex13, and pex14. Moreover, with regard to peroxisome membrane assembly, we showed that Pex19p functions in the cytosol as a chaperone for membrane proteins and translocates them to peroxisome membrane by docking to Pex3p. Our most recent findings include the regulation of peroxisome morphogenesis. We found that peroxisome morphogenesis is regulated by Pex11p, Fis1, ad DLP1 in a concerted manner.

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (52 results)

All 2007 2006 2005 2004 2003 Other

All Journal Article (46 results) Book (1 results) Publications (5 results)

  • [Journal Article] Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis.2007

    • Author(s)
      Kobayashi, S. et al.
    • Journal Title

      Experimental Cell Research 313 (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fis1,DLP1,and Pex11p coordinately regulate peroxisome morphogenesis.2007

    • Author(s)
      Kobayashi, S., et al.
    • Journal Title

      Experimental Cell Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis2007

    • Author(s)
      Kobayashi, S. et al.
    • Journal Title

      Experimental Cell Research 313(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p.2006

    • Author(s)
      Matsuzono Y. et al.
    • Journal Title

      Journal of Biological Chemistry 281(1)

      Pages: 36-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex.2006

    • Author(s)
      Furuki S. et al.
    • Journal Title

      Journal of Biological Chemistry 281(3)

      Pages: 1317-1323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional domains and dynamic assembly of the peroxin Pex14p, the entry site of matrix proteins.2006

    • Author(s)
      Ito R., Fujiki Y.
    • Journal Title

      Journal of Biological Chemistry 281(15)

      Pages: 10196-10205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Peroxisome division is impaired in a CHO cell mutant with an inactivating point-mutation in dynamin-like protein 1 gene.2006

    • Author(s)
      Tanaka A. et al.
    • Journal Title

      Experimental Cell Research 312(9)

      Pages: 1671-1684

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A temperature-sensitive CHO pex1 mutant with a novel mutation in the AAA Walker A1 motif.2006

    • Author(s)
      Fan W., Fujiki Y.
    • Journal Title

      Biochemical and Biophysical Research Communications 345(4)

      Pages: 1434-1439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional domain mapping of peroxin Pex19p : interaction with Pex3p is essential for function and translocation.2006

    • Author(s)
      Matsuzono Y. et al.
    • Journal Title

      Journal of Cell Science 119(17)

      Pages: 3539-3550

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p.2006

    • Author(s)
      Tamura S. et al.
    • Journal Title

      Journal of Biological Chemistry 281(38)

      Pages: 27693-27704

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular mechanisms of import of peroxisome-targeting signal type 2 (PTS2) proteins by PTS2 receptor Pex7p and PTS1 receptor Pex5pL.2006

    • Author(s)
      Mukai S., Fujiki Y.
    • Journal Title

      Journal of Biological Chemistry 281(49)

      Pages: 37311-37320

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lessons from peroxisome-deficient Chinese hamster ovary (CHO) cell mutants.2006

    • Author(s)
      Fujiki Y. et al.
    • Journal Title

      Biochimica et Biophysica Acta - Molecular Cell Reserach 1763(12)

      Pages: 1374-1381

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Import of peroxisomal membrane proteins : The interplay of Pex3p- and Pex19p-mediated interactions.2006

    • Author(s)
      Fujiki Y. et al.
    • Journal Title

      Biochimica et Biophysica Acta - Molecular Cell Reserach 1763(12)

      Pages: 1639-1646

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pexl9p.2006

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

      Journal of Biological Chemistry 281

      Pages: 36-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pexlp x Pex6p complex.2006

    • Author(s)
      Furuki, S., et al.
    • Journal Title

      Journal of Biological Chemistry 281

      Pages: 1317-1323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional domains and dynamic assembly of the peroxin Pexl4p, the entry site of matrix proteins.2006

    • Author(s)
      Ito, R., Fujiki, Y.
    • Journal Title

      Journal of Biological Chemistry 281

      Pages: 10196-10205

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Peroxisome division is impaired in a CHO cell mutant with an inactivating point-mutation in dynamin-like protein 1 gene.2006

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

      Experimental Cell Research 312

      Pages: 1671-1684

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A temperature-sensitive CHO pexl mutant with a novel mutation in the AAA Walker Al motif.2006

    • Author(s)
      Fan, W., Fujiki, Y.
    • Journal Title

      Biochemical and Biophysical Research Communications 345

      Pages: 1434-1439

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional domain mapping of peroxin Pex19p : interaction with Pex3p is essential for function and translocation.2006

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

      Journal of Cell Science 119

      Pages: 3539-3550

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dynamic and functional assembly of the AAA peroxins, Pexlp and Pex6p, and their membrane receptor Pex26p.2006

    • Author(s)
      Tamura, S., et al.
    • Journal Title

      Journal of Biological Chemistry 281

      Pages: 27693-27704

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular mechanisms of import of peroxisome-targeting signal type 2 (PTS2) proteins by PTS2 receptor Pex7p and PTS1 receptor Pex5pL.2006

    • Author(s)
      Mukai, S., Fujiki, Y.
    • Journal Title

      Journal of Biological Chemistry 281

      Pages: 37311-37320

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lessons from peroxisome-deficient Chinese hamster ovary (CHO) cell mutants.2006

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

      Biochimica et Biophysica Acta-Molecular Cell Research 1763

      Pages: 1374-1381

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Import of peroxisomal membrane proteins : The interplay of Pex3p-and Pexl9p-mediated interactions.2006

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

      Biochimica et Biophysica Acta-Molecular Cell Research 1763

      Pages: 1639-1646

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional domains and Dynamic Assembly of the Peroxin Pex14p, the Entry Site of Matrix Proteins2006

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

      The Journal of Biological Chemistry 281(5)

      Pages: 10196-10205

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Peroxisome division is impaired in a CHO cell mutant with an inactivating point-mutation in dynamin-like protein 1 gene2006

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

      Experimental Cell Research 312(9)

      Pages: 1671-1684

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A temperature-sensitive CHO pexl mutant with a novel mutation in the AAA Walker A1 motif2006

    • Author(s)
      Fan, W.et al.
    • Journal Title

      Biochemical and Biophysical Research Communication 345(4)

      Pages: 1434-1439

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Functional domain mapping of peroxin Pex19p : interaction with Pex3p is essential for function and translocation2006

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

      Journal of Cell Science 119(17)

      Pages: 3539-3550

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dynamic and Functional Assembly of the AAA Peroxins, Pex1p and Pex6p, and Their Membrane Receptor Pex26p2006

    • Author(s)
      Tamura, S. et al.
    • Journal Title

      The Journal of Biological Chemistry 281(38)

      Pages: 27693-27704

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Molecular Mechanisms of Import of Peroxisome- targeting Signal Type 2 (PTS2) Proteins by PTS2 Receptor Pex7p and PTS1 Receptor Pex5pL2006

    • Author(s)
      Mukai, S. et al.
    • Journal Title

      The Journal of Biological Chemistry 281(49)

      Pages: 37311-37320

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lessons from peroxisome-deficient Chinese hamster ovary (CHO) cell mutants2006

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

      Biochimica et Biophysica Acta-Molecular Cell Research 1763(12)

      Pages: 1374-1381

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Import of peroxisomal membrane proteins : the interplay of Pex3p- and Pex19p- mediated interactions2006

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

      Biochimica et Biophysica Acta-Molecular Cell Research 1763(12)

      Pages: 1639-1646

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Functional domains and dynamic assembly of the peroxin pex14p, the entry site of matrix proteins2006

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

      Journal of Biological Chemistry (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Peroxisome division is impaired in a CHO cell mutant with an inactivating point-mutation in cynamin-like protein 1 gene2006

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

      Experimental Cell Research (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with Pex1p-Pex6p complex2006

    • Author(s)
      Furuki, S. et al.
    • Journal Title

      Journal of Biological Chemistry 281(3)

      Pages: 1317-1323

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p2006

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

      Journal of Biological Chemistry 281(1)

      Pages: 36-42

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5 : ATP-independent import and ATP-dependent export.2005

    • Author(s)
      Miyata N., Fujiki Y.
    • Journal Title

      Molecular and Cellular Biology 25(24)

      Pages: 10822-10832

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5 : ATP-independent import and ATP-dependent export.2005

    • Author(s)
      Miyata, N., Fujiki, Y.
    • Journal Title

      Molecular and Cellular Biology 25

      Pages: 10822-10832

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: ATP-independent import and ATP-dependent export2005

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

      Molecular and Cellular Biology 25(24)

      Pages: 10822-10832

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Overexpression of human acyl-CoA thioesterase upregulates peroxisome biogenesis.2004

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Experimental Cell Research 297(1)

      Pages: 127-141

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of human acyl-CoA thioesterase unregulates peroxisome biogenesis.2004

    • Author(s)
      Ishizuka, M., et al.
    • Journal Title

      Experimental Cell Research 297

      Pages: 127-141

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of human acyl-CoA thioesterase upregulates peroxisome biogenesis.2004

    • Author(s)
      Ishizuka, M.et al.
    • Journal Title

      Experimental Cell Research 297

      Pages: 127-141

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ペルオキシソームの形成機構とペルオキシソーム病2004

    • Author(s)
      藤木 幸夫
    • Journal Title

      蛋白質核酸酵素 増刊号

      Pages: 1136-1142

    • NAID

      10006343568

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The pathogenic peroxin Pex26p recruits the Pexlp-Pex6p AAA ATPase complexes to peroxisomes.2003

    • Author(s)
      Matsumoto N. et al.
    • Journal Title

      Nature Cell Biology 5(5)

      Pages: 454-460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation.2003

    • Author(s)
      Matsumoto N. et al.
    • Journal Title

      American Journal of Human Genetics 73(2)

      Pages: 233-246

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The pathogenic peroxin Pex26p recruits the Pexlp-Pex6p AAA-ATPase complexes to peroxisomes.2003

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

      Nature Cell Biology 5

      Pages: 454-460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations in novel peroxin gene PEX26 that cause peroxisome biogenesis disorders of complementation group 8 provide a genotype- phenotype correlation.2003

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

      American Journal of Human Genetics 73

      Pages: 233-246

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] The World of the Cell(日本語翻訳版)2005

    • Author(s)
      Becker, W.M.et al.
    • Publisher
      西村書店(in press)
    • Related Report
      2004 Annual Research Report
  • [Publications] Tanaka, A.: "cDNA cloning and characterization of the third isoform of human peroxin Pex11p."Biochemical and Biophysical Research Communications. 300. 819-823 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsumoto, N.: "The novel pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA-ATPase complexes to peroxisomes"Nature Cell Biology. 5. 454-460 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsumoto, N.: "Mutations in novel peroxin gene PEX26 that cause peroxisome biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation"The American Journal of Human Genetics. 73. 233-246 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujiki, Y.: "Functional Complementation"Cooper DN (ed.) Nature : Encyclopedia of the Human Genome. 2. 539-543 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujiki, Y.: "Peroxisome Biogenesis Disorders"Cooper DN (ed.) Nature : Encyclopedia of the Human Genome. 4. 541-547 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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