1998 Fiscal Year Final Research Report Summary
Cloning of gene (s) controlloing the size of mitochondria in mammalian cells
| Project/Area Number |
09670152
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
WAKABAYASHI Takashi School of Medicine, Nagoya University Professor, 医学部, 教授 (00079998)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Megamitochondria / mmm1 / mdm10 / Culture cells / Free radicals / Apoptpsis |
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| Research Abstract |
We hypothesize concerning the mechanism of the megamitochondria (MG) formation that there exhists gene(s) in mammalian cells homologous to those identified in yeast cells, mmm1, mdm10, Which control the size and distribution of mitochondria (Mit) in the cell and that the modification of such gene(s) by free radicals might result in the formation of MG.Data obtained during '97-'98 and future studies : 1. Transfection of RL-34 and MDCK cells with mmm1 or mdm10 : Expression of these genes was proved by a laser conforcal microscope. The establishment of the permanent cell line is now in progress. 2. Interactions between the cytoskeleton and Mit : We have found that in normal RL-34 and MDCK cells filamentous Mit stained with CMXRos have the closest aposition to actin filaments among various components of cytoskeleton and that Mit become granular surrounding the nucleus when actin is depolymerized. Research on the interaction among Mit, cytoskeleton and free radicals are now in progress. 3. Establishment of the model for the MG formation in culture cells and the role of free radicals as a common mediator of MG formation : We have succeeded in inducing MG by H_2O_2 besides chemicals capable of generationg free radicals while they are metabolized. Also, free, radical-induced MG formations were suppressed by scavenger of free radicals. 4. MG formation is followed by apoptosis : We have found that cells in the prsence of MG become apoptotic with time. We have disclosed first in the literature the pathophysiological meaning of the phenomenon of the formation of MG.We are studying the details in the correlation between the MG formation and apoptosis.
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[Publications] Karbowski, M., Kurono, C., Wozniak, M., Ostrowski, M., Teranishi, M.Soji, T.and Wakabayashi, T.: "Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria." Biochim.Biophys.Acta. 144. 25-40 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Karbowski, M., Kurono, C., Wozniak, M., Ostrowski, M., Teranishi, M., Nishizawa, Y., Usukura, J., Soji, T.and Wakabayashi, T.: "free radical-induced megamitochondria formation and apoptosis." Free Rad.Biol.Med.26. 396-409 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kamimoto, T., Nagai, Y., Onogi, H., Muro, Y., Wakabayashi, T.and Hagiwara, M.: "Dymple, a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammalian cells." J.Biol.Chem.273. 1044-1051 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsuhashi, T., Karbowski, M., Liu, XR., Usukura, J., Nishizawa, Y., Wozniak, M.and Wakabayashi, T.: "Complete suppression of ethanol-induced formation of megamitochondria by 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl(4-OH-TEMPO)." Free Rad.Biol.Med.24. 139-147 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Karbowski, M., Kurono, C., Nishizawa, Y., Horie, Y., Soji, T.and Wakabayashi, T.: "Induction of megamitochondria by some chemicals inducing oxidative stress in primary cultured rat hepatocytes." Biochim.Biophys.Acta. 1349. 242-250 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Wakabayashi, T., Adachi, K., Matsuhashi, T., Wozniak, M., Antosiewicz, J.and Karbowski, M.: "Suppression of the formation of megamitochondria by scavengers for free radicals." Molec.Aspects Med.18(Suppl). 51-61 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsuhashi, T., Liu, XR., Nishizawa, Y., Karbowski, M., Antosiewicz, J.and Wakabayashi, T.: "Role of free radicals in the mechanism of the hydrazine-induced formation of megamitochodnria." Free Rad.Biol.Med.23. 285-293 (1997)
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「研究成果報告書概要(欧文)」より
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