EXPLORING ASSEMBLY &FUNCTION OF CAF4 COMPLEX & ITS ROLE IN MITOCHONDRIAL FISSION

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• 批准号: 7725071
• 负责人: KARI NAYLOR
• 金额: $ 1.49万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725071
• 关键词: Affect; Autosomal Dominant Optic Atrophy; Blindness; Cell physiology; Cells; Childhood; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Equilibrium; Event; Funding; Grant; Institution; Instruction; Maintenance; Mediating; Microscopy; Mitochondria; Mitochondrial Diseases; Production; Proteins; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Structure; Textbooks; Tubular formation; United States National Institutes of Health; bean; insight; loss of function

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mitochondria are the powerhouse of the cell, producing the bulk of the ATP energy necessary for cellular function. The production of this ATP energy is dependent upon the maintenance of a specialized mitochondrial structure. Textbooks often simplistically present this structure to look like a jelly bean; however, mitochondria are actually tubular and highly branched. This specialized tubular structure is maintained by complementary fusion and fission events during which two mitochondria merge into one, or one mitochondrion divides into two, respectively. These events must be balanced because too much of either fission or fusion can alter the structure of the mitochondria, potentially resulting in loss of function and leading to diseases such as dominant optic atrophy, a disease causing childhood blindness. To understand the regulation of mitochondrial structure this project focuses on a recently identified protein  Caf4  and its role in mitochondrial fission. Three proteins, Dnm1, Mdv1, and Fis1 mediate the physical division of the mitochondrial tubule. While some of the steps that take place to mediate the actual division event are well understood, it is not known what instructs the mitochondria to divide. We hypothesize that Caf4 may transmit this signal or instruction to the other proteins. Using fluorescent microscopy we propose to determine Caf4's function in mitochondrial division, specifically determining if Caf4 instructs Dnm1, Mdv1, and Fis1 to activate. Understanding Caf4's function in mitochondrial division will provide valuable insight into how the regulation of mitochondrial structure affects mitochondrial function and, in turn, help us understand mitochondrial diseases.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 线粒体是细胞的发电站，产生细胞功能所需的大部分ATP能量。 这种ATP能量的产生依赖于一种特殊的线粒体结构的维持。 教科书通常简单地将这种结构呈现为看起来像果冻豆;然而，线粒体实际上是管状和高度分支的。 这种特殊的管状结构是通过互补的融合和分裂事件来维持的，在此期间，两个线粒体合并为一个，或者一个线粒体分裂为两个。 这些事件必须平衡，因为过多的裂变或融合会改变线粒体的结构，可能导致功能丧失并导致疾病，如显性视神经萎缩，这是一种导致儿童失明的疾病。 为了了解线粒体结构的调节，该项目将重点放在最近鉴定的蛋白质上  咖啡4  以及它在线粒体分裂中的作用 三种蛋白质Dnm 1、Mdv 1和Fis 1介导线粒体小管的物理分裂。 虽然一些介导实际分裂事件的步骤已经被很好地理解，但还不知道是什么指示线粒体分裂。 我们假设Caf 4可能将此信号或指令传递给其他蛋白质。使用荧光显微镜，我们建议确定Caf 4在线粒体分裂中的功能，特别是确定Caf 4是否指示Dnm 1，Mdv 1和Fis 1激活。 了解Caf 4在线粒体分裂中的功能将为线粒体结构的调节如何影响线粒体功能提供有价值的见解，进而帮助我们了解线粒体疾病。