Human mitochondrial ACP interactions

7.项目摘要。线粒体损伤和线粒体脂肪酸合酶（mtFAS）疾病 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 然而，这一结论最近受到质疑， 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， mtFAS在线粒体代谢途径中起着更大的作用。mtACP调节的层次结构， 从线粒体蛋白质翻译到呼吸复合体组装， 这种控制的分子基础仍不清楚。该计划旨在应用新的化学，结构， 生物物理工具，以了解酰基-mtACP如何在线粒体代谢中相互作用。鉴于 线粒体在细胞代谢中的核心作用，这一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，治疗 线粒体疾病

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.