Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm

合作研究：定义一种重要的、保守的蛋白质的功能，该蛋白质将线粒体基质与细胞质独特地连接起来

基本信息

批准号：
2215728
负责人：
Magdalena Bezanilla
金额：
$ 63.85万
依托单位：
Dartmouth College
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2026-07-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2215728&HistoricalAwards=false
关键词：
Collaborative Research Defining functions essential

项目摘要

Complex organisms, including humans, other animals, and plants, depend on chemical energy produced in their cells by tiny cellular substructures called mitochondria that consume oxygen and release CO2. This project investigates a specific component of mitochondria essential to their function. Plants depend on photosynthesis in chloroplasts and respiration in mitochondria to convert electron transport energy to chemical energy. While the importance of photosynthesis is well recognized, the contribution of plant mitochondrial respiration is underappreciated, even though 25 to 50% of CO2 converted to sugars by photosynthesis is released as CO2. Defining mechanisms controlling mitochondrial function are therefore critical to plant growth and productivity. This project will uncover the mechanistic details of mitochondrial function. The Broader Impacts of the work include the intrinsic merit of the research as mitochondria ultimately contribute to plant productivity and CO2 release which are issues critical to agriculture and climate change. Additional activities include enhancing diversity in the STEM workforce through developing a "Biotech at San Diego State University" Scholars Program (BT@SDSU) that will involve all PIs that are part of this collaborative project. The program includes intensive lab research experiences and summer internships in biotech companies along with an ongoing scholars community focused on learning strategies and skills for career preparedness. Through continuous program improvement, BT@SDSU will serve as a model for other programs to support students who want to enter biotech careers.This project will investigate how specific mitochondrial components integrate mitochondrial function with the rest of the plant cell, which has required the evolution of communication pathways across the mitochondrial membrane. This important question will be addressed through studies of the ATAD3 proteins (ATPase family AAA domain-containing protein 3) in plants. These mitochondrial proteins span from the matrix to the cytosol, across both the inner and outer mitochondrial membranes, uniquely positioning them to integrate mitochondrial function within the cell. They combine a distinct C-terminal AAA+ domain located in the mitochondrial matrix and an N-terminal ATAD3-N domain of unknown function that is exposed to the cytosol. Although linked to many mitochondrial processes, their biochemical and cellular functions remain unknown. This research seeks to understand how the AAA+ and ATAD3-N domains contribute to the essential roles of ATAD3. The project will not only uncover functions of these conserved proteins that are essential to life, but also provide new insights into how ATAD3s have evolved in the plant lineage to integrate mitochondria into the cell while training the next generation of biotech researchers.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.

复杂的生物，包括人类，其他动物和植物，取决于其细胞在其细胞中所产生的化学能，该化学能被称为线粒体，可消耗氧和释放二氧化碳。该项目研究了线粒体对其功能必不可少的特定组成部分。植物依赖于叶绿体中的光合作用和线粒体的呼吸，以将电子传输能量转化为化学能。尽管光合作用的重要性得到了充分的认可，但植物线粒体呼吸的贡献不足，尽管通过光合作用将25％至50％的二氧化碳转化为糖，以CO2释放。因此，定义控制线粒体功能的机制对于植物生长和生产力至关重要。该项目将揭示线粒体功能的机械细节。这项工作的更广泛的影响包括研究的内在优点，因为线粒体最终有助于植物生产力和二氧化碳释放，这对农业和气候变化至关重要。其他活动包括通过开发“圣地亚哥州立大学生物技术”学者计划（BT@SDSU）来增强STEM劳动力的多样性，该计划将涉及所有是该协作项目的一部分的PI。该计划包括强化实验室研究经验和生物技术公司的暑期实习，以及持续的学者社区，专注于学习策略和技能以进行职业准备。通过持续的计划改进，BT@SDSU将作为其他计划的模型，以支持想要进入生物技术职业的学生。本项目将研究特定的线粒体组件如何将线粒体功能与其他植物细胞相结合，该植物细胞需要在整个线粒体膜上进行通信途径的演变。这个重要的问题将通过对植物中ATAD3蛋白（AAA AAA域的AAA域蛋白3）的研究来解决。这些线粒体蛋白质从基质到细胞质跨越内部和外部线粒体膜，独特地定位它们以在细胞中整合线粒体功能。它们结合了位于线粒体基质中的不同的C末端AAA+结构域和暴露于细胞质的N端ATAD3-N域的N端ATAD3-N结构域。尽管与许多线粒体过程相关，但它们的生化和细胞功能仍然未知。这项研究试图了解AAA+和ATAD3-N领域如何促进ATAD3的基本作用。该项目不仅将发现这些对生命必不可少的蛋白质的功能，而且还将提供新的见解，以了解ATAD3在植物谱系中如何发展的，以将线粒体整合到细胞中，同时培训下一代生物技术研究人员。该奖项反映了NSF的法定任务，并通过评估商标来反映出支持者的支持者，并通过评估商标进行了支持。