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

哺乳动物细胞心磷脂功能的遗传学和生物化学研究

• 批准号: 05671862
• 负责人: NISHIJIMA Masahiro
• 金额: $ 1.28万
• 依托单位: National Institute of Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671862/
• 关键词: somatic cell mutant; phosphatidylglycerol; cardiolopin; mitochondria; electron transport system; PGP synthase; cloning

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.

磷脂酰甘油磷酸（PGP）合酶催化参与磷脂酰甘油合成的反应，磷脂酰甘油充当仅在真核细胞的线粒体膜中发现的心磷脂的代谢前体。我们分离出一种中国仓鼠卵巢细胞突变体，该突变体在体外的PGP合成酶活性和在体内的磷脂酰甘油和心磷脂的合成中具有温度依赖性缺陷，并且对细胞生长具有温度敏感性。当磷脂酰甘油和心磷脂水平降低时，该突变体不仅具有线粒体的形态异常，而且具有线粒体的功能异常，表现为耗氧量和ATP产生减少，糖酵解增加，以及在葡萄糖缺乏培养基中细胞生长的更严格的温度敏感性。这些结果构成了遗传证据，表明PGP合酶是细胞生长所必需的，心磷脂在线粒体功能中起着关键作用。

项目成果

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)

Toshiaki Ohtsuka、Masahiro Nishijima、Kenji Suzuki 和 Yuzuru Akamatsu：“缺乏钙磷脂的培养中国仓鼠细胞突变体的线粒体功能障碍”J.Biol.Chem.268。

Toshiaki Ohtsuka: "Mitochondrial dysfunction of a unltured chinese hamster ovory cell mutant deficient in cardiolipin" J.Biol.Chem.268. 22914-22919 (1993)

Toshiaki Ohtsuka：“缺乏心磷脂的未培养的中国仓鼠卵巢细胞突变体的线粒体功能障碍”J.Biol.Chem.268。

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 (19

Kentaro Hanada、Kiyo Izawa、Masahiro Nishijima 和 Yuzuru Akamatsu：“鞘脂缺乏会导致 CD14（一种糖基磷脂酰肌醇锚蛋白）对磷脂酰肌醇特异性磷脂酶 C 过敏”J.Biol.Chem.268。

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-

Nishijima，M.，Hara-kuges.，Takasuka，N.，Akakawa，K.，Setouchi，M.，Matuura，K.，Yamamoto，S.和Akamatsu，Y.：“生化莱斯隆的鉴定和特征

Masahiro Nishijima,Kentaro Hanada,and Yuzuru Akamatsu: "Genetic and Biochemical Approaches to understanding Biosynthesis and Functions of Sphingolipids" The FASEB J.8. A1258- (1994)

Masahiro Nishijima、Kentaro Hanada 和 Yuzuru Akamatsu：“了解鞘脂生物合成和功能的遗传和生化方法”FASEB J.8。