RUI: Exploring the Function of FtsZs and the Cytoskeleton to Determine the Molecular Mechanism of Mitochondrial Dynamics in Dictyostelium discoideum

细胞线粒体调节许多过程，如钙水平和程序性细胞死亡。然而，它们以能量转导而闻名，通常被称为细胞的发电站。 这个项目的重点是线粒体结构，因为没有适当的结构，线粒体变得功能失调。 虽然线粒体是从祖先细菌细胞发展而来的，但不同的生物体（例如，人类、变形虫、藻类、酵母等）以不同的方式维持线粒体结构。 如果我们能够理解维持这些生物体结构的机制，我们就可以了解为什么这些机制是不同的，同时也可以深入了解线粒体功能障碍的原因。这个项目的更广泛的影响包括这项工作的内在价值，因为绝大多数真核细胞都含有这些细胞器。 其他活动将涉及K-16学生。 阿肯色州中部一所以本科为主的大学的学生将实施这一项目。 接触高质量，资金充足的研究为学生提供了探索研究是否适合他们的职业选择的能力。它为博士课程的学生做好准备，指导学生进行研究对于保留那些传统上在STEM中代表性不足的群体至关重要。 除了培训本科生外，该项目还涉及向K-6学生推广。 该计划是正式与当地小学的关系，特别是那些ACT Aspire分数显示科学赤字的学校。 通过实践活动与K-6学生的互动旨在激励学生，向他们展示科学是有趣的，并继续发展他们的科学探究技能。线粒体的基本功能取决于其结构，而结构又取决于线粒体动力学、分裂、融合和运动。 在许多细胞类型中，如哺乳动物和酵母细胞，一个被称为动力蛋白相关蛋白（DRPs）的蛋白质家族维持着高度互连的线粒体网络。重要的是，我们的模式生物盘基网柄藻不使用DRPs来调节线粒体动力学。 相反，D. discoideum基因组编码两种蛋白质FszA和FszB，它们来源于细菌细胞分裂蛋白FtsZ。 目前还不清楚为什么有些生物使用DRP，有些生物使用似乎是衍生的FtsZ蛋白。 本研究的一个长期目标是了解线粒体动力学的分子机制。discoideum，以确定何时以及为什么一些生物体在进化过程中用DRP取代FtsZ。第一个项目的目标是确定现存的FtsZs在线粒体动力学中的作用，并将涉及改变蛋白质水平，识别相互作用的蛋白质，并分析FtsZs结构复合物。最近的工作表明，细胞骨架是线粒体动力学调节的主要参与者，该项目的第二个目标是通过识别分裂/融合事件沿着细胞骨架被破坏时的运输速度来研究细胞骨架与线粒体动力学的关系。这个项目的完成将有助于确定FtsZ是否像DRP一样发挥作用，以及D。盘状细胞骨架调节线粒体动力学。最后，这项工作将有助于理解线粒体的进化和线粒体动力学，特别是为什么有些生物使用DRPs，有些使用FtsZ。该项目由分子和细胞生物科学部和刺激竞争研究计划（EPSCoR）联合资助该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查进行评估，被认为值得支持的搜索.

Cellular mitochondria regulate many processes, such as calcium levels and programmed cell death. However, they are best known for energy transduction and are often referred to as the powerhouse of the cell. This project focuses on mitochondrial structure because without appropriate structure, mitochondria become dysfunctional. Although mitochondria developed from an ancestral bacterial cell, different organisms (e.g., humans, amoeba, algae, yeast, etc.) maintain mitochondrial structure in different ways. If we can understand the mechanisms that maintain structure across these organisms, we can learn why the mechanisms are different while also gaining insight into the causes of mitochondrial dysfunction. The broader impacts of this project include the intrinsic merit of the work as the vast majority of eukaryotic cells contain these organelles. Other activities will involve K-16 students. Students at a primarily undergraduate university in central Arkansas will carry out this project. Exposure to quality, well-funded research provides students the ability to explore whether research is an appropriate career choice for them. It prepares students for doctoral programs, and mentoring students in research is critical for retention of those from groups traditionally underrepresented in STEM. In addition to training undergraduates, this project involves outreach to K-6 students. The plan is to formalize relationships with local elementary schools, specifically ones whose ACT Aspire scores indicate a deficit in science. Interactions with K-6 students via hands-on-activities are designed to inspire students, show them that science is fun, and continue to develop their scientific inquiry skills. The essential functions of the mitochondria are dependent upon their structure, which, in turn, is dependent upon mitochondrial dynamics, fission, fusion, and motility. In many cell types such as mammalian and yeast cells, a protein family known as dynamin-related proteins (DRPs) maintains the highly interconnected network of mitochondria. Importantly, our model organism, Dictyostelium discoideum does not use DRPs to regulate mitochondrial dynamics. Rather, the D. discoideum genome encodes two proteins, FszA and FszB, which are derived from the bacterial cell division protein, FtsZ. It is not understood why some organisms use DRPs and some use what appears to be derived FtsZ proteins. A long-term goal of this research is to understand the molecular mechanism of mitochondrial dynamics in D. discoideum in order to identify when and why some organisms replaced FtsZs with DRPs as they evolved. The first project goal is to identify the role of extant FtsZs in mitochondrial dynamics and will involve altering protein levels, identifying interacting proteins, and analyzing FtsZs structural complexes. Recent work has shown that the cytoskeleton is a major player in the regulation of mitochondrial dynamics, and the second goal of this project is to study the relationship of the cytoskeleton with mitochondrial dynamics by identifying fission/fusion events, along with transport velocities when the cytoskeleton is disrupted. Completion of this project will help determine if FtsZs function like DRPs, and how the D. discoideum cytoskeleton regulates mitochondrial dynamics. Ultimately, this work will contribute to understanding the evolution of mitochondria and mitochondrial dynamics and specifically why some organisms use DRPs and some use FtsZs.This project is jointly funded by the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competititive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.