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

• 批准号: 2215727
• 负责人: Elizabeth Vierling
• 金额: $ 76.56万
• 依托单位: University of Massachusetts Amherst
• 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 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2215727&HistoricalAwards=false
• 关键词: Collaborative; Research; Defining; functions; essential

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.

复杂的生物体，包括人类、其他动物和植物，依赖于细胞中被称为线粒体的微小细胞亚结构产生的化学能，线粒体消耗氧气并释放二氧化碳。该项目研究了线粒体的一种对其功能至关重要的特定成分。植物依靠叶绿体的光合作用和线粒体的呼吸作用将电子传递能转化为化学能。虽然光合作用的重要性已被充分认识，但植物线粒体呼吸的贡献被低估了，尽管光合作用转化为糖的CO2中有25%至50%以CO2的形式释放。因此，确定控制线粒体功能的机制对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制细节。 这项工作的更广泛影响包括这项研究的内在价值，因为线粒体最终有助于植物生产力和二氧化碳释放，而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，该计划将涉及作为该合作项目一部分的所有PI。该计划包括密集的实验室研究经验和生物技术公司的暑期实习，沿着一个持续的学者社区，专注于学习策略和职业准备技能。通过持续的项目改进，BT@SDSU将成为其他项目的典范，以支持希望进入生物技术职业的学生。该项目将研究特定的线粒体成分如何将线粒体功能与植物细胞的其他部分整合在一起，这需要线粒体膜上的通讯途径的进化。这一重要问题将通过对植物中ATAD 3蛋白（ATP酶家族AAA结构域蛋白3）的研究来解决。这些线粒体蛋白质跨越线粒体内膜和线粒体外膜，从基质到胞质溶胶，独特地定位它们以整合细胞内的线粒体功能。它们联合收割机了位于线粒体基质中的独特C-末端AAA+结构域和暴露于胞质溶胶的未知功能的N-末端ATAD 3-N结构域。虽然与许多线粒体过程有关，但它们的生物化学和细胞功能仍然未知。本研究旨在了解AAA+和ATAD 3-N结构域如何有助于ATAD 3的重要作用。该项目不仅将揭示这些对生命至关重要的保守蛋白质的功能，还将为ATAD 3如何在植物谱系中进化以将线粒体整合到细胞中提供新的见解，同时培训下一代生物技术研究人员。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。