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Genetic and biocheminal atudy on the function of cardiolipin in mammlian cells

Research Project

Project/Area Number 05671862
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionNational Institute of Health

Principal Investigator

NISHIJIMA Masahiro  NIH,Director, 細胞化学部, 部長 (60072956)

Co-Investigator(Kenkyū-buntansha) SAITO Kyoko  NIH,Researcher, 細胞化学部, 研究員 (70235034)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordssomatic cell mutant / phosphatidylglycerol / cardiolopin / mitochondria / electron transport system / PGP synthase / cloning
Research Abstract

Phosphatidylglycerophosphate (PGP) synthase catalyzes a reaction involved in the synthesis of phosphatidylglycerol which serves as a metablic precursor for cardiolipin found exclusively in mitochondrial membranes of eukaryotic cells. We isolated a Chinese hamster ovary cell mutant with temperature-dependent defects both in PGP synthase adtivity in vitro and in the synthesis of phosphatidylglycerol and cardiolipin in vivo, together with temperature-sensitivity for cell growth. When phosphatidylglycerol and cardiolipin levels were reduced, this mutant possessed not only morphological but also functional abnormalities of mitochondria, manifested by reduced oxygen consumption and ATP production, increased glycolysis, and more stringent temperature-sensitivity for cell growth in glucose-deficientmedium. These results constitute genetic evidence that PGP synthase is essential for cell growth and that cardiolipin plays a critical rote in mitochondrial functions.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Toshiaki Ohtsuka,Masahiro Nishijima,and Yuzuru Akamatsu: "A Sowatic Cell Mutant Defective in Phosphatidylglycerophosphate Synthase,with Iwpaired Phosphatidylglycerol and Caldidipin Biosynthesis" J.Biol.Chem.268. 22908-22913 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiaki Ohtsuka,Masahiro Nishijima,Kenji Suzuki,and Yuzuru Akamatsu: "Mitochondrial Dysfunction of a cultured Chinese Hamster overy Cell Mutant Deficient in Caldiolipin" J.Biol.Chem.268. 22914-22919 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kentaro Hanada,Kiyo Izawa,Masahiro Nishijima and Yuzuru Akamatsu: "Sphingolipid Deficiency Induces Hypersensitivity of CD14,a Glycosyl Phosphatidylinositol-auchored Protein,to Phosphatidylinositol-Specific Phospholipase C" J.Biol.Chem.268. 13820-13823 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masahiro Nishijima,Kentaro Hanada,and Yuzuru Akamatsu: "Genetic and Biochemical Approaches to understanding Biosynthesis and Functions of Sphingolipids" The FASEB J.8. A1258- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishijima,M.,Hara-kuges.,Takasuka,N.,Akagawa,K.,Setouchi,M.,Matuura,K.,Yamamoto,S.,and Akamatsu,Y.: "Identification of a Biochemical Leslon,and Characteristic Response to Lipopolysaccharide(LPS)of a cultured Macrophage-Like Cell Mutant with Defective LPS-Binding" J.Biochem.116. 1082-1087 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Pugin J.,Heumann D.,Tomasz,A.,Krakhenko.V.V.,Akamatsu,Y.,Nishijima,M.,Glauser,U.P.,Tobias,P.S.,and Ulevitch,R.J.: "CD14 Is a Pattern Recognition Receptor" Immunity. 1. 509-516 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 西島正弘: "臨床検査" 医学書院, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 花田賢太郎・西島正弘: "医学のあゆみ" 医歯薬出版(株), (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jerome Pugin: "CD14 Is a Pattern Recognition Receptor" Immunity. 1. 509-516 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masahiro Nishijima: "Identification of a Biochornical Lesion and Choracteristic Reysonse to Lipopoly saicharide(LPS) of a Cultared Macrophage Like Cell Mutant with Defective LPS-Binding" J.Biochem.116. 1082-1087 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kentaro Hanada: "Both Sphingolipids and Chotestert Participate in the Detergent Insolubility of Alkaline Phosphatase,a Blycosyl phosphatidylinostol-anchored Protein,in Mammalisn Membranes" J.Biol.Chem.270(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toshiaki Ohtsuka: "A somatic cell mutant defectivein pfosphatilyglycerophosphate synthase,with impaired phosphutidylglyceol and cardiolipin biosynthesis" J.Biol.Chem.268. 22908-22913 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Toshiaki Ohtsuka: "Mitochondrial dysfunction of a unltured chinese hamster ovory cell mutant deficient in cardiolipin" J.Biol.Chem.268. 22914-22919 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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