CAREER: Investigation of the Cellular and Physiological Effects of Chloroplast/Mitochondrial Iron Export in Plants

该奖项全部或部分根据2021年美国救援计划法案（公法117- 2）资助铁是几乎所有生命形式（包括植物）所需的矿物质营养素。然而，当铁在细胞或生物体内过量或不适当地分布时，铁是有毒的。为了科普这种矛盾，生物体已经进化出精密的策略来严格控制铁。揭示铁调节的过程将产生生物学的基础知识。与此同时，缺铁是一个严重的公共卫生问题，影响着全球近一半的人口。主食作物不是铁的丰富来源，是全世界铁的主要膳食来源。因此，要可持续地解决铁营养不良问题，必须了解植物铁调节的分子机制，并将这些知识应用于生物强化，即通过选择性育种或基因工程提高作物营养价值的过程。该项目的重点是研究植物线粒体和叶绿体中的铁调节，线粒体和叶绿体是植物代谢的核心，需要高水平的铁来发挥作用。该项目的预期成果将提供具有重要科学价值的知识和重要见解，可用于改善农业和人类健康。此外，为加强本科生的真实研究经验而建议的教育活动，以及为K-12推广的社区学习非主要生物课程，将促进下一代科学家和科学传播者的成长。线粒体和叶绿体是需要铁的重要代谢过程的场所。这些细胞器还参与感知铁和整合信号，以协调对铁水平变化的代谢和生理反应。与此同时，铁必须在线粒体和叶绿体中受到严格控制，因为它们在有氧条件下容易受到铁失调的高度反应性所造成的损害。本项目通过研究拟南芥线粒体和叶绿体铁输出缺陷突变体，研究植物线粒体和叶绿体中的铁调节及其在细胞和生理水平上的影响。具体而言，异常膜内陷检测铁缺乏突变体缺陷的线粒体和叶绿体铁输出将进行分析，以测试的假设，这些结构有助于细胞间的铁运输使用细胞生物学和先进的成像技术。膜运输尚未在线粒体和叶绿体铁的背景下进行研究，并将推进我们对植物铁稳态的分子机制的理解。叶绿体/线粒体铁出口商和蛋白质，螯合铁在叶绿体和线粒体之间的潜在功能相互作用也将使用分子遗传学，生物化学和蛋白质组学方法进行研究。这样的分析将提供关键的知识在线粒体和叶绿体的细胞器间铁稳态。总的来说，这个项目结合了多学科的方法，将有助于更全面地了解植物铁稳态。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2) Iron is a mineral nutrient required for virtually all forms of life, including plants. However, iron is toxic when present in excess or improperly distributed within the cell or the organism. To cope with such paradox, organisms have evolved delicate strategies to tightly control iron. Uncovering the processes of iron regulation will generate knowledge fundamental to biology. Meanwhile, iron deficiency is a serious public health issue that affects nearly half of the global population. Staple crops, which are not rich sources of iron, are the main dietary source of iron worldwide. Therefore, to sustainably solve iron malnutrition, it is essential to understand the molecular mechanisms of iron regulation in plants and apply the knowledge for biofortification, the process of enhancing nutritional value of crops via selective breeding or genetic engineering. This project focuses on investigating iron regulation in plant mitochondria and chloroplasts, which are specialized intracellular compartments central to plant metabolism and require high levels of iron for their function. The expected outcomes of this project will provide knowledge significant for its scientific merit and critical insights that can be applied to improve agriculture and human health. Furthermore, the proposed educational activities to enhance authentic research experience for undergraduate students and the community-based learning non-major biology course for K-12 outreach will foster the growth of next generation scientists and science communicators.Mitochondria and chloroplasts are the site of vital metabolic processes that require iron. These organelles are also involved in sensing iron and integrating signals to coordinate metabolic and physiological responses to changes in iron levels. Meanwhile, iron must be tightly controlled in the mitochondria and chloroplasts, as they are prone to damage caused by the highly reactive nature of dysregulated iron under aerobic conditions. This project investigates iron regulation in plant mitochondria and chloroplasts, and its impact at the cellular and physiological levels, by examining Arabidopsis mutants defective in exporting iron from the mitochondria and chloroplasts. Specifically, abnormal membrane invaginations detected in iron-deficient mutants defective in mitochondrial and chloroplast iron export will be analyzed to test the hypothesis that these structures contribute to intercellular iron transport using cell biology and advanced imaging techniques. Membrane trafficking has not been previously studied in the context of mitochondrial and chloroplast iron and will advance our understanding of the molecular mechanisms of plant iron homeostasis. The potential functional interactions between the chloroplast/mitochondrial iron exporter and proteins that sequester iron in chloroplasts and mitochondria will also be investigated using molecular genetics, biochemistry, and proteomic approaches. Such analyses will provide critical knowledge on inter-organellar iron homeostasis in mitochondria and chloroplasts. Overall, this project incorporates multi-disciplinary approaches and will contribute towards a more comprehensive understanding of plant iron homeostasis.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.