1990 Fiscal Year Final Research Report Summary
Cloning Regulatory Genes for Proliferation of Mitochondria and Effects on Mitochondrial Disease
| Project/Area Number |
01570141
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Jichi Medical School |
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Principal Investigator |
OHTA Shigeo Jichi Medical School, Department of Biochemistry, Assistant Professor, 医学部, 講師 (00125832)
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| Project Period (FY) |
1989 – 1990
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| Keywords | mitochondria / ATP synthase / mitochondrial encephalomyopathy / transcriptional control / gene cloning |
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| 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.
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[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)
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「研究成果報告書概要(和文)」より
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[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)
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「研究成果報告書概要(和文)」より
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[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)
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「研究成果報告書概要(和文)」より
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[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)
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「研究成果報告書概要(和文)」より
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[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"
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「研究成果報告書概要(和文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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