Fundamental mechanisms of apoptosis and phospholipid asymmetry

细胞凋亡和磷脂不对称的基本机制

基本信息

批准号：
10084175
负责人：
DING XUE
金额：
$ 2.1万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

项目摘要

Project summary Programmed cell death, phospholipid asymmetry, and paternal mitochondrial elimination are three vitally important, distinct, and interconnected biological processes essential for normal cell functions and animal development. Defects in these processes can cause various pathological conditions and human disease, including neurodegenerative disease, autoimmune disorders, various inherited human mitochondrial disease, and cancer. In this proposed work, we will carry out molecular genetic, reverse genetic, biochemical, cell biological, biophysical, and functional genomic analyses to decipher basic mechanisms of apoptosis, phospholipid asymmetry, and paternal mitochondrial elimination during animal development. For the study of apoptosis, we hope to understand the regulatory mechanisms and signaling pathways that control the release of mitochondrial apoptogenic factors during apoptosis and identify new targets and downstream pathways of the cell death protease that execute highly organized cell disassembly and rapid removal of the dying cells. For the study of phospholipid asymmetry, we plan to identify the molecular components and regulatory machineries that generate, maintain, and alter phospholipid asymmetry, decipher the functions and roles of specific phospholipids to a cell, and reveal the physiological and pathological consequences of altered phospholipid asymmetry to the cell and the animal. For the study of paternal mitochondrial elimination, we will investigate how and why paternal mitochondria are selectively recognized and targeted for elimination, the paternal and maternal factors and machineries required of this uniparental inheritance process, and the physiological significance of paternal mitochondrial elimination to embryo development and organismal fitness. These studies should reveal novel mechanisms, pathways, and genes that control these three fundamental biological processes, and ultimately, provide new targets, ideas, and strategies to facilitate treatment of numerous human diseases caused by abnormalities in these three important processes.

项目摘要程序性细胞死亡，磷脂不对称和父亲线粒体消除是三个至关重要的重要的，独特的和相互联系的生物学过程，对正常细胞功能和动物必不可少发展。这些过程中的缺陷会导致各种病理状况和人类疾病，包括神经退行性疾病，自身免疫性疾病，各种遗传的人线粒体疾病，和癌症。在这项提出的工作中，我们将进行分子遗传，反向遗传，生化，细胞生物学，生物物理和功能性基因组分析，以破译凋亡的基本机制，在动物发育过程中，磷脂不对称和父亲线粒体消除。为了研究凋亡，我们希望了解控制释放的调节机制和信号传导途径凋亡过程中线粒体凋亡因素的执行高度有组织的细胞分解并快速去除垂死细胞的细胞死亡蛋白酶。为了磷脂不对称的研究，我们计划确定分子成分和调节产生，维护和改变磷脂不对称的机器，破译的功能和作用对细胞的特定磷脂，并揭示了改变的生理和病理后果对细胞和动物的磷脂不对称。为了研究父亲的线粒体消除，我们将研究如何选择性地识别和瞄准父亲线粒体以消除这种单亲继承过程需要的父亲和母体因素和机器以及父亲线粒体消除对胚胎发育和有机健康的生理意义。这些研究应揭示控制这三个基本的新型机制，途径和基因生物过程，最终提供了新的目标，思想和策略，以促进治疗这三个重要过程中由异常引起的许多人类疾病。