Fundamental mechanisms of paternal mitochondrial eliminationand radiation-induced bystander effects

R35 GM118188(雪、派) 项目名称 父本线粒体消除的基本机制和辐射诱导的旁观者效应 项目总结 父本线粒体消除和辐射诱导的旁观者效应是两个至关重要的、截然不同的、 以及对动物发育、应激反应和机体健康至关重要的动态生物过程。 这两个重要过程中的缺陷会导致各种病理状况和疾病。在这 拟开展的工作包括分子遗传学、反向遗传学、生物化学、细胞生物学和蛋白质组学 解读调节父本线粒体消除和辐射诱导的基本机制的分析 旁观者效应。为了研究父亲的线粒体消除，我们希望了解父亲是如何 线粒体在受精卵中选择性地受损、识别和移除，父系和母系是什么 机制被用来特定地消除父亲的线粒体，以及为什么父亲的线粒体需要 被移除以确保动物发育以及细胞和器官的健康。为了研究辐射- 诱导旁观者效应，我们计划在未曝光的情况下确定触发旁观者效应的因素 细胞、介导不同旁观者反应的信号通路以及旁观者的机制基础 对其他压力的反应。这些研究应该揭示控制的新机制、途径和基因 这两个基本的生物过程，并最终提供了新的目标，想法和战略，以 促进治疗由父系线粒体消除异常引起的多种人类疾病 并通过减少放射治疗和其他治疗方法引起的副作用来改进疾病治疗 治疗。

Summary of R35 GM118188 (Xue, PI) Project title Fundamental mechanisms of paternal mitochondrial elimination and radiation-induced bystander effects Project summary Paternal mitochondrial elimination and radiation-induced bystander effects are two vitally important, distinct, and dynamic biological processes essential for animal development, stress response, and organismal fitness. Defects in these two important processes can cause various pathological conditions and disease. In this proposed work, we will carry out molecular genetic, reverse genetic, biochemical, cell biological and proteomic analyses to decipher basic mechanisms that regulate paternal mitochondrial elimination and radiation-induced bystander effects. For the study of paternal mitochondrial elimination, we hope to understand how paternal mitochondria are selectively impaired, recognized and removed in fertilized eggs, what paternal and maternal mechanisms are employed to specifically eliminate paternal mitochondria, and why paternal mitochondria need to be removed to ensure animal development and cell and organismal fitness. For the study of radiation- induced bystander effects, we plan to identify factors involved in triggering bystander effects in unexposed cells, signal pathways that mediate different bystander responses, and the mechanistic basis of bystander responses to other stresses. These studies should reveal novel mechanisms, pathways, and genes that control these two fundamental biological processes, and ultimately, provide new targets, ideas, and strategies to facilitate treatment of numerous human diseases caused by abnormalities in paternal mitochondrial elimination and improve disease treatment by reducing side effects caused by radiotherapy and other therapeutic treatments.