酿酒酵母天冬半胱氨酸酶依赖型和非依赖型凋亡分子机制的研究

项目名称： 酿酒酵母天冬半胱氨酸酶依赖型和非依赖型凋亡分子机制的研究

项目编号： No.31301020

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 崔逸仙

作者单位： 清华大学

项目金额： 25万元

中文摘要： 凋亡是一种重要的细胞程序性死亡方式，在多细胞生物的生长发育，肿瘤的形成，神经退行性疾病等过程中有着至关重要的作用。近来发现在单细胞生物中也存在着与多细胞生物中十分相似的细胞凋亡方式, 但其凋亡机制研究得远不如在多细胞生物中的清楚。根据多细胞生物中凋亡的研究,可将凋亡分为天冬半胱氨酸酶（caspase）依赖型和非依赖型两大类。虽然在哺乳动物细胞中对caspase依赖型途径研究较多，但对酵母中的caspase所知甚少。本申请计划利用酵母这一重要的分子遗传学模式生物，寻找酵母凋亡中新的潜在的caspase，并研究其在凋亡中的作用机制，补充在哺乳动物细胞中进行的凋亡研究。另外，对caspase非依赖型的凋亡方式研究，整体还很不透彻，本申请计划在本实验室的研究基础上进一步研究由酵母AMID类似物(NADH脱氢酶Ndi1)所介导的caspase非依赖型凋亡途径的分子机制，希望可补充对这一途径的理解。

中文关键词： 酵母；凋亡；天冬半胱氨酸酶；Ndi1；Yca1

英文摘要： Apoptosis is a mode of programmed cell death that is essential for the development of multicellular organisms, the progression of tumor and neurodegenerative disorders and so on. Recently，apoptosis is also found in unicellular organisms and the phenotype is quite similar with that in metazoan organisms. However, the apoptotic molecular mechanism in unicellular organism is still unclear. The apoptotic pathways can be divided into two kinds, the one is caspase-dependent, the other is caspase-independent, based on whether caspases are involved in or not. Although, the caspase-mediated pathways in mammalian cells are largely studied, little is known in yeast. To complement the study, the present proposal is planned to identify new potential caspases in yeast using this powerful molecular model organism. Furthermore, the study on caspase-independent pathway is also gravely lack. We want to know more about this by investigating the molecular mechanism of yeast AMID homologue, NADH dehydrogenase Ndi1, promoted caspase-independent apoptotic cell death, providing valuable clues and theoretical supports for curing critical diseases caused by dysregulations in apoptosis.

英文关键词： yeast；apoptosis；caspase；Ndi1；Yca1