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Cloning Regulatory Genes for Proliferation of Mitochondria and Effects on Mitochondrial Disease

Research Project

Project/Area Number 01570141
Research Category

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

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionJichi Medical School

Principal Investigator

OHTA Shigeo  Jichi Medical School, Department of Biochemistry, Assistant Professor, 医学部, 講師 (00125832)

Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsmitochondria / ATP synthase / mitochondrial encephalomyopathy / transcriptional control / gene cloning / 遺伝子 / 遺伝子発現 / ヒト / 転写制御因子
Research Abstract

The system coordinating expressions of nuclear coded mitochondrial proteins was investigated by examination of the 5'-flanking region of the human mitochondrial ATP synthase beta-subunit gene.
At least two regions enhanced this promoter activity and at least one region repressed it. In one of the enhancing regions, a consensus sequence was found for the genes of other mitochondrial proteins such as those for cytochrome c1 and the pyruvate dehydrogenase alpha-subunit. This enhancing activity was independent of the orientation or location of the insert. Therefore, this is an enhancer that may be common to the nuclear genes of some mitochondrial proteins involved in energy transduction.
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is a major heterogeneous mitochondrial diseases. For identifying a mutation in the mitochondrial gene, we isolated myogenic cell lines with distinctly different phenotypes from the same muscle tissue from a patient with MELAS : one was respiratory-deficient and the other was apparently normal.
Only one A to G nucleotide transition at nucleotide number 3.243 in the tRNA-Leu (UUR) gene was found in whole mitochondrial DNA of the respiratory-deficient cells compared with that of the normal cells. This mutation was also found in 8 patients from unrelated families with MELAS in a heteroplasmic manner, but not in control individuals. Therefore, the single point mutation causes the functional abnormality in respiratory chain of mitochondria.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Kagawa,Y.and Ohta,S.: "Regulation of mitochondrial ATP sythesis in mammlian cells by transcriptional control." Int.J.Biochem.,. 22. 219-229 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tomura,H.,Endo,H.,Kagawa,Y.and Ohta,S.: "Regulatory enhancer in the nuclear gene for the human mitochondrial ATP synthase beta subunit" J.Biol.Chem.,. 265. 6525-6527 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hayashi,J.Tanaka,M.,Sato,W.,Ozawa,Kagawa,Y.and Ohta,S.: "Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclearーcoded subunits of complexes involved in the oxidative phosphorylation" Biochem.Biophys.Res.Commun.167. 216-211 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ostuka,M.,Niijima,K.,Mizuno,Y.,Yoshida,M.,Kagawa,Y.,and Ohta,S.: "Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy." Biochem.Biophys.Res.Commun.167. 680-685 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohta,S.,Harada,M.,Ito,Y.,Kabayashi,Y.,Sone,N.,and Kagawa,Y.: "The alpha 1 beta 1 heteroologomer of ATP synthase" Biochem.,Biophys.Res.Commun.171. 1258-1263 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kobayashi,Y.,Momoi,M.,Tominaga,K.,Nihei,K.,Yanagisawa,M.,Kagawa,Y.and Ohta,S.: "A point mutation in the mitochondrial tRNAーLeu(UUR) gene in MELAS (mitochondrial myopathy,encephalopathy,lactic acidosis and strokeーlike episodes)" Biochem.Biophys.Res.Commun.173. 816-822 ( 990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shimoizumi,H.,Momoi,M.,Ohta,S.,Kagawa,Y.,Momoi,T.,and Yanagisawa,M.: "Cytochrome c oxidaseーdeficient myogenic cell lines in mitochondrial myopathy." Ann Neurol. 25. 615-621 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kagawa,Y.,Ohta,S.,Yohda,M.,Hamamoto,T.,and Hirata,H.: "Biotechnological applications of thermophilic ATP synthase" J.Membrane Biol.41. 237-247 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Endo,H,Miyabayashi,S.,Hasegawa,K.,Narisawa,K.Kagawa,Y.and Ohta S.: "Cloning of a defective gene encoding the pyruvate dehydrogenase^2 E1 alpha subunit from a patient with deficiency" J.Inher.Metab.Dis.12. 363-367 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohta,S.,Endo,H.,Matsuda,K.,Kagawa,Y.and Ohta,S.: "Gene structure of the promoter region for the human pyruvate dehydrogenase E1 alpha subunit gene"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yuzaki,M.,Ohkoshi,N.,Kanazawa,I.,Kagawa,Y.,: "Multiple deletions in mitochondrial DNA at direct repeats of nonーDーloop regions in cases of familial mitochondrial myopathy." Biochem.Biophys.Res.Commun.164. 1352-1357 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "ミトコンドリアの形成制御とその病態分子遺伝子" 遺伝. 43. 45-50 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "ミトコンドリアATP合成系の形成とその制御" 生化学. 61. 75-88 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "ミトコンドリアのATP合成酵素とその遺伝子" 代謝. 26. 29-38 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "ミトコンドリア脳筋症の一年間の進展" 実験医学. 7. 175-177 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "PCR法と遺伝子診断" 代謝. 27. 297-303 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 太田 成男: "ミトコンドリア脳筋症の解析" 実験医学. 8. 1086-1089 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Endo,H.,Hasegawa,K.,Narisawa,K.,Tada,K.,Kagawa,Y.and Ohta,S.: "Defective gene of lactic acidosis: Abnormal pyruvate dehydrogenase E1 alpha subunit caused by a frame shift"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kagawa, Y. and Ohta S.: "Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control" Int. J. Biochem. 22. 219-229 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tomura, H., Endo, H., Kagawa, Y. and Ohta, S.: "Regulatory enhancer in the nuclear gene for the human mitochondrial ATP synthase beta subunit" J. Biol. Chem. 265. 6525-6527 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hayashi, J., Tanaka, M., Sato, W., Ozawa, K., Kagawa, Y. and Ohta, S.: "Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclear-coded subunits of complexes involved in the oxidative phosphorylation" Biochem. Biophys. Res. Commun.167. 216-221 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Otska, M., Nijima, K., Mizuno, Y., Yoshida, M. Kagawa, Y. and Ohta, S.: "Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy." Biochem. Biophys. Res. Commun.167. 680-685 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohta, S., Harada, M., Io, Y., Kobayashi, Y., Sone, N. and Kagawa, Y.: "The alpha 1 beta 1 heterooligomer of ATP synthase" Biochem. Biophys. Res. Commun.171. 1258-1263 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kobayashi, Y., Momoi, M., Tominaga, K., Nihei, K., Yanagisawa, M., Kagawa, Y. and Ohta, S.: "A point mutation in the mitochondrial tRNA-Leu(UUR) gene in MELAS(mitochondrial myopathy, encepholopathy, lactic acidosis and stroke-like episodes)" Biochem. Biophys. Res. Commun.173. 816-822 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yuzaki, M., Ohkoshi, N., Kanazawa, I., Kagawa, Y. and Ohta, S.: "Multiple deletions in mitochodrial DNA at direct repeats of non-D-1oop regions in cases of familial mitochodrial myopathy." Biochem. Biphys. Res. Commun.164,. 1352-1357 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Endo, H., Hasegawa, K., Narisawa, K., Tada, K., Kagawa, Y. and Ohta, S.: "Defective gene of lactic acidosis, Abnormal pyruvate dehydrogenase E1 alpha subunit caused by a frame shift" Am. J. Hum. Genetics.44,. 358-364 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shimoizumi, H., Momoi, M., Ohta, S., Kagawa, Y., Momoi, T., Yanagisawa, M.: "Cytochrome c oxidase-deficient myogenic cell lines in mitochondrial myopathy." Ann. Neurol.25,. 615-621 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohta, S., Endo, H., Matsuda, K. and Kagawa, Y.: "Gene structure of the promoter region for the human pyruvate dehydrogenase E1 alpha subunit" Ann. NY Acad. Sci.573,. 438-440 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kagawa,Y.and Ohta,S.: "Regulation of mitochondrial ATP sythesis in mammalian cells by transcriptional control." Int.J.Biochem.,. 22. 219-229 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tomura,H.,Endo,H.,Kagawa,Y.and Ohta,S.: "Regulatory enhancer in the nuclear gene for the human mitochondrial ATP synthase subunit" J.Biol.Chem.,. 265. 6525-6527 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hayashi,J.Tanaka,M.,Sato,W.,Ozawa,Kagawa,Y.and Ohta,S.: "Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclearーcoded subunits of complexes involved in the oxidative phosphorylation" Biochem.Biophys.Res.Commun. 167. 216-221 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ostuka,M.,Niijima,K.,Mizuno,Y.,Yoshida,M.,Kagawa,Y.and Ohta,S.: "Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy." Bjochem.Biophys.Res.Commun.167. 680-685 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ohta,S.,Harada,M.,Ito,Y.,Kabayashi,Y.,Sone,N.,and Kagawa,Y.: "The alpha l heteroolgomer of ATP synthase" Biochem.,Biophys.Res.Commun.171. 1258-1263 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kobayashi,Y.,Momoi,M.,Tominaga,K.,Nihei,K.,Yanagisawa,M.,Kagawa,Y.and Ohta,S.: "A point mutation in the mitochondrial tRNAーLeu(UUR)gene in MELAS(mitochondral myopathy,encephathy,lactic acidosis and strokeーlike episodes)" Biochem.Biophys.Res.Commun.173. 816-822 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 遠藤仁司: "Defective gene of lactic acidosis;Abnormal pyruvate dehydrogenase El alpha subunit caused by a frame shift" Am.J.Hum.Genet.44. 358-364 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 下泉秀夫: "Cytochrome c oxidase-deficient myogenic cell lines in mitochondrial myopathy" Ann.Neurol.25. 615-621 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 香川靖男: "Biotechnological applications of thermophilic ATP synthase" J.Membrane Sci.41. 237-247 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 遠藤仁司: "Cloning of a defective gene encoding the pyruvate dehydrogenase El alpha subunit from a patient with its deficiency" J.Inher.Metab.Dis.12. 363-367 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 香川靖男: "Alpha3 beta3 complex of thermophilic ATP synthase" FEBS lett.249. 67-69 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "Gene structure of the promoter region for pyruvate dehydrogenase El alpha subunit" Ann.New York Acad.Sci.573. 458-460 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 林純一: "Effects of Ethidium Bromide Treatment on the gene expression of mammalian mitochordrial proteins." Biochem.Biophys.Res.Comm.

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "ミトコンドリア病-最近注目される呼吸鎮酵素の欠損を中心とした疾患" 化学と生物. 27. 78-79 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "ミトコンドリア脳筋症の一年間の進展" 実験医学. 7. 175-177 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 香川靖男: "ミトコンドリアのATP合成酵素とその遺伝子" 代謝. 26. 29-38 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 香川靖男: "ミトコンドリアATP合成系の形成とその制御" 生化学. 61. 75-88 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "DNAポリメラ-ゼ増幅法(PCR法)の応用" 細胞工学. 8. 545-553 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 水野美邦: "Deficiencies in Complex I subunits of the respiratory chain in Parkinson's disease" Biochem.Biophys.Res.Comm.163. 1450-1455 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 柚崎通介: "Multiple deletions in mitochondrial DNA at direct repeats of non-D-loop regions in cases of familial mitochondrial myopathy" Biochem.Biophys.Res.Comm.164. 1352-1357 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 香川靖男: "Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control" Int.J.Biochem.

    • Related Report
      1989 Annual Research Report
  • [Publications] 伊藤雄司: "Small-angle neutron scattering studies of the reconstituted TFl of H^+-ATPase from thermophilic bacterium PS3 with deuterated subunits" J,Mol.Biol.

    • Related Report
      1989 Annual Research Report
  • [Publications] 戸村秀明: "Novel regulatory enhancer in the nuclear gene for the human ATP synthase beta subunit." J.Biol.Chem.

    • Related Report
      1989 Annual Research Report
  • [Publications] 大塚美恵子: "Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy" Biocem.Biophys.Res.Comm.

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "ミトコンドリアの形成制御とその病態分子遺伝学" 遺伝. 43. 45-50 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "PCR法の遺伝子診断への応用" 代謝. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "CDNAクロ-ニング用ラムダファ-ジベクタ-" 実験医学.

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "ミトコンドリア脳筋症の解析" 実験医学.

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "直接シ-クエンス法" 実験医学.

    • Related Report
      1989 Annual Research Report
  • [Publications] 太田成男: "PCR(polymerage chain reaction)原理とその幅広い応用" 医学界新聞. 1886. 3-3 (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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