Roles of mitochondrial proteins in regulations of energy metabolism and apoptosis

线粒体蛋白在能量代谢和细胞凋亡调节中的作用

• 批准号: 14370746
• 负责人: SHINOHARA Yasuo
• 金额: $ 8.83万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370746/
• 关键词: mitochondria; apoptosis; permeability transition; cytochrome c; proteomics analysis; energy conversion; Yeast; 酸化的リン酸化; 遺伝子壊変酵母; エネルギー変換; アポトーシス

Mitochondria are known to be a major site of cellular energy conversion. However, recent studies demonstrated that mitochondria are not only functioning as a site of energy conversion, but also as a regulatory site of cellular fate. Control of cellular fate by mitochondria is known to be regulated by controlling the release of mitochondrial cytochrome c into the cytosol. When cellular signals of apoptosis are delivered into the mitochondria, dysfunction of mitochondria is induced and mitochondrial cytochrome c is released from mitochondria. Cytochrome c thus released into cytosol triggers subsequent steps of cellular apoptosis. However, mechanisms how mitochondrial cytochrome c is released from mitochondria are still uncertain.In the present study, to understand the molecular mechanisms controlling release of mitochondrial cytochrome c, relationship between mitochondrial dysfunction and release of mitochondrial cytochrome c was investigated. As a result, release of mitochondrial cytochrome c was found to be independent process from the dysfunction of mitochondria.Furthermore, to understand the roles of mitochondrial proteins in the regulation of release of mitochondrial cytochrome c, experimental system using yeast cells was established. Our results clearly indicated that yeast mitochondria could be utilize as a nice model system of mammalian mitochondria, because dysfunction of yeast mitochondria caused release of mitochondrial cytochrome c likewise mammalian mitochondria.

线粒体是细胞能量转换的主要部位。然而，最近的研究表明，线粒体不仅作为能量转换的场所，而且作为细胞命运的调节场所。已知线粒体对细胞命运的控制是通过控制线粒体细胞色素c释放到细胞质中来调节的。当细胞凋亡信号被传递到线粒体时，线粒体功能障碍被诱导，线粒体细胞色素c从线粒体中释放出来。细胞色素c因此释放到细胞质中触发细胞凋亡的后续步骤。然而，线粒体细胞色素c从线粒体中释放的机制尚不清楚。为了了解线粒体细胞色素c释放的分子机制，本研究探讨了线粒体功能障碍与线粒体细胞色素c释放的关系。结果发现线粒体细胞色素c的释放是一个独立于线粒体功能障碍的过程。此外，为了了解线粒体蛋白在线粒体细胞色素c释放调控中的作用，我们建立了酵母细胞实验系统。我们的结果清楚地表明酵母线粒体可以作为哺乳动物线粒体的一个很好的模型系统，因为酵母线粒体功能障碍引起线粒体细胞色素c的释放，哺乳动物线粒体也是如此。

项目成果

Three-way effect of cyanine dye on the structure and function of mitochondria

花青染料对线粒体结构和功能的三向效应

• 发表时间: 2003
• 期刊: J. Health Sci. 49
• 作者: Tominaga;K.;Kondo;C.;Kagata;T.;Hishida;T.;Nishizuka;M.;Imagawa;M.;K.Yamashita et al.
• 通讯作者: K.Yamashita et al.

Permeability transition-independent release of mitochondrial cytochrome c induced by valinomycin

缬氨霉素诱导的线粒体细胞色素 c 的通透性转变独立释放

• 发表时间: 2002
• 期刊: Eur. J. Biochem. 269
• 作者: Y.Shinohara et al.

Close location of the first loop to the third loop of the mitochondrial ADP/ATP carrier deduced from cross-linking catalyzed by copper-c-phenanthroline of the solubilized carrier with Triton X-100

由溶解载体的铜-c-菲咯啉与 Triton X-100 催化交联推断出线粒体 ADP/ATP 载体的第一环与第三环的位置接近

• 发表时间: 2002
• 期刊: J.Biochem. 131
• 作者: E.Majima;M.Takeda;S.Miki;Y.Shinohara;H.Terada
• 通讯作者: H.Terada

Y.Shinohara, M.R.Almofti, T.Yamamoto, T.Ishida, F.Kita, H.Kanazaki, M.Ohnishi, K.Yamashita, S.Shimizu, H.Terada: "Permeability transition-independent release of mitochondrial cytochrome c induced by valinomycin"Eur.J.Biochem.. 269. 5224-5230 (2002)

Y.Shinohara、M.R.Almofti、T.Yamamoto、T.Ishida、F.Kita、H.Kanazaki、M.Ohnishi、K.Yamashita、S.Shimizu、H.Terada：“线粒体细胞色素 c 诱导的渗透性转变独立释放

K.Kajimoto, T.Daikoku, F.Kita, N.Yamazaki, M.Kataoka, Y.Baba, H.Terada, Y.Shinohara: "PCR-select subtraction for characterization of messages remarkably expressed in brown adipose tissue"Mol.Gen.Metabol.. 80. 255-261 (2003)

K.Kajimoto、T.Daikoku、F.Kita、N.Yamazaki、M.Kataoka、Y.Baba、H.Terada、Y.Shinohara：“用于表征在棕色脂肪组织中显着表达的信息的 PCR 选择扣除”Mol。