Functional Profiling to Identify Mitochondria-cell Signaling Networks

 描述（由申请人提供）：线粒体是复杂的细胞器，在多种重要细胞过程中发挥重要作用，包括对环境污染物的反应。线粒体生物学的一个未被充分认识的方面是线粒体和细胞之间的通信在调节细胞对暴露于环境污染物的反应中发挥的关键作用。我们对导致和导致线粒体信号传导的细胞过程和途径的不完全理解继续阻碍对环境暴露于污染物的功能后果的评估。因此，我们提出了一个全面的功能方法来定义线粒体信号转导中涉及的保守毒性途径。我们将利用酵母，酿酒酵母和人类之间的基本细胞过程的进化保守性，结合酵母中独特的功能分析方法，以确定参与线粒体信号转导的保守过程。我们将首先使用选定的毒物验证我们的方法，随后使用酵母中可能的高通量筛选方法来筛选多种环境毒物，以全面定义线粒体信号转导途径。

 DESCRIPTION (provided by applicant): Mitochondria are complex organelles which play major roles in multiple vital cellular processes including response to environmental contaminants. An underappreciated aspect of mitochondrial biology is the key role that communication between the mitochondria and the cell plays in modulating cellular response to exposure to environmental contaminants. Our incomplete understanding of the cellular processes and pathways which lead to and result from mitochondrial signaling continues to hamper assessment of the functional consequences of environmental exposure to contaminants. We are therefore proposing a comprehensive functional approach to define the conserved toxicity pathways involved in mitochondrial signaling. We will take advantage of the evolutionary conservation of basic cellular processes between yeast, Saccharomyces cerevisiae, and humans in conjunction with unique functional profiling approaches in yeast to identify the conserved processes involved in mitochondrial signaling. We will first validate our approach using selected toxicants and subsequently use high throughput screening approaches possible in yeast to screen a diversity of environmental toxicants to comprehensively define the pathways of mitochondrial signaling.