Human mitochondrial ACP interactions

人类线粒体 ACP 相互作用

• 批准号: 10469436
• 负责人: Michael D. Burkart
• 金额: $ 19.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469436
• 关键词: Acyl Carrier Protein; Adopted; Aging; Amino Acid Motifs; Amino Acid Sequence; Anabolism; Arginine; Behavior; Binding; Biochemical; Biochemical Pathway; Biogenesis; Biology; Calorimetry; Caprylates; Chemicals; Complex; Cryoelectron Microscopy; Data; Deposition; Differential Scanning Calorimetry; Disease; Enzymes; Escherichia coli; Event; Fatty Acids; Fatty-acid synthase; Goals; Health; Human; Interferometry; Iron; Knowledge; Label; Length; Leucine; Lipids; Maintenance; Metabolic Pathway; Metabolism; Methods; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Molecular; Molecular Conformation; NADH dehydrogenase (ubiquinone); Neurodegenerative Disorders; Pathway interactions; Peripheral; Play; Post-Translational Protein Processing; Production; Property; Proteins; Reactive Oxygen Species; Regulation; Reporting; Ribosomes; Role; Scaffolding Protein; Series; Structure; Substrate Interaction; Substrate Specificity; Sulfur; Surface Plasmon Resonance; System; Technology; Thioctic Acid; Titrations; Translating; Translations; Tyrosine; Validation; age related; analog; base; biophysical techniques; biophysical tools; cysteine desulfurase; disease phenotype; genetic regulatory protein; mitochondrial metabolism; polyketide synthase; programs; protein protein interaction; respiratory; skills; tool

7. Project Summary. Mitochondrial damage, and mitochondrial fatty acid synthase (mtFAS) disorders in particular, have been associated with aging and neurodegenerative disease. Historically these disorders were attributed to a decrease in lipoic acid production, however, this conclusion has recently come into question with the growing evidence that the mitochondrial acyl carrier protein (mtACP), the substrate-shuttling protein of mtFAS, plays a much greater role within mitochondrial metabolic pathways. A hierarchy of mtACP regulation, from mitochondrial protein translation to respiratory complex assembly, has been recently revealed, however the molecular basis of such control remains unclear. This program aims to apply new chemical, structural, and biophysical tools to understand how acyl-mtACP interacts within the mitochondrial metabolism. Given the central role of the mitochondria in cellular metabolism, this program will fundamentally impact our understanding of aging and health maintenance and provide potential new avenues to treatment of mitochondrial diseases.

7.项目总结。线粒体损伤和线粒体脂肪酸合成酶(MtFas)紊乱 特别是与衰老和神经退行性疾病有关。从历史上看，这些疾病是 然而，由于硫辛酸产量的减少，这一结论最近受到了质疑 越来越多的证据表明，线粒体酰基载体蛋白(MtACP)，底物穿梭蛋白 线粒体Fas在线粒体代谢途径中起着重要的作用。MtACP监管的层级， 然而，最近发现了从线粒体蛋白质翻译到呼吸复合体组装的过程 这种控制的分子基础仍不清楚。该计划旨在应用新的化学品，结构和 了解酰基-mtACP如何在线粒体代谢中相互作用的生物物理工具。给定 线粒体在细胞新陈代谢中的核心作用，这个计划将从根本上影响我们的 了解衰老和健康维护，并提供潜在的新途径的治疗 线粒体疾病。