STUDYING FSZA TO ELUCIDATE THE LINK BETWEEN PROKARYOTES AND MITOCHONDRIA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 线粒体是动态细胞器，其通过产生和维持管状结构的裂变和融合事件持续经历膜重塑，从而允许线粒体区室有效地响应细胞的代谢需要。这项研究的重点是了解线粒体裂变的机制，这似乎是人类的一个重要过程。在线粒体从原核生物祖先进化的过程中，一些原始的真核生物，包括盘基网柄藻，保留了祖先的线粒体分裂机制。我们的总体目标是揭示D中的裂变机制。discoideum和追踪高等真核线粒体和它们的原核祖先之间的进化联系。前体细胞分裂由FtsZ介导，FtsZ组装成一个环，将细胞收缩并分裂成两个子细胞。明显失去FtsZ蛋白的真核生物，如酵母，使用发动蛋白相关蛋白（DRPs）来介导线粒体分裂。D. discoideum表达至少两种FtsZ直系同源物（FszA和FszB），并且似乎通过FtsZ型机制介导其线粒体小管的分裂，可能与DRP型机制结合。深入了解真核生物线粒体裂变需要了解所有的裂变机制，包括D。盘状突我们推测FszA及其蛋白伴侣在D.通过收缩和分裂线粒体小管来控制盘状突。为了验证这一假设，我们提出了一种新的在体内显微镜为基础的系统来调查裂变事件在D。在真实的时间（具体目标1）和识别裂变机制的组成部分（具体目标2）。 最终，拟议研究的结果将有助于我们理解线粒体分裂，这是维持管状线粒体结构所必需的过程。这种结构的破坏已被证明会导致发育缺陷，导致神经退行性疾病，并影响程序性细胞死亡的调节。了解真核生物中线粒体分裂的分子机制将有助于我们了解细胞凋亡的过程，并开发各种线粒体疾病的治疗方法。因此，了解维持线粒体结构的过程对人类健康很重要。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mitochondria are dynamic organelles that continually undergo membrane remodeling by fission and fusion events that create and maintain the tubular structure, allowing the mitochondrial compartment to efficiently respond to metabolic needs of the cell. The proposed study focuses on understanding the mechanisms of mitochondrial fission, which appears to be an essential process in humans. During the evolution of mitochondria from prokaryotic ancestors, several primitive eukaryotic organisms, including Dictyostelium discoideum, retained the ancestral mechanism to divide their mitochondria. Our overall goal is to uncover the fission mechanism in D. discoideum and trace the evolutionary link between higher eukaryotic mitochondria and their prokaryotic ancestors. Prokaryotic cell division is mediated by FtsZ, which assembles into a ring that constricts and splits the cell into two daughter cells. Eukaryotes, such as yeast, that have apparently lost FtsZ proteins use dynamin-related proteins (DRPs) to mediate mitochondrial division. D. discoideum expresses at least two FtsZ orthologs (FszA and FszB) and appears to mediate division of its mitochondrial tubules by an FtsZ-type mechanism, possibly in conjunction with a DRP-type mechanism. A thorough understanding of eukaryotic mitochondrial fission requires knowledge of all fission mechanisms, including the rudimentary mechanisms used in D. discoideum. We hypothesize that FszA, together with its protein partners, plays a direct role in mitochondrial fission in D. discoideum by constricting and dividing the mitochondrial tubule. To test this hypothesis, we propose to develop a novel in vivo microscopy-based system to investigate fission events in D. discoideum in real time (Specific Aim 1) and to identify components of fission machinery (Specific Aim 2). Ultimately, the results of the proposed study will contribute to our understanding of mitochondrial fission, a process necessary for maintaining the tubular mitochondrial structure. Disruption of this structure has been shown to cause developmental defects, lead to neurodegenerative diseases, and affect regulation of programmed cell death. Understanding the molecular mechanisms of mitochondrial fission in eukaryotes will help us to understand the cellular process of apoptosis and develop treatments for a variety of mitochondrial diseases. Thus, understanding the processes that maintain mitochondrial structure is important to human health.