Metabolic Regulation of Mitochondrial Function

线粒体功能的代谢调节

• 批准号: 10624517
• 负责人: Gulcin Pekkurnaz
• 金额: $ 27.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10624517
• 关键词: Architecture; Biochemical Pathway; Biochemistry; Bioenergetics; Cells; Chemicals; Dimensions; Disease; Endocrine System Diseases; Energy Supply; Enzymes; Eukaryotic Cell; Goals; Heterogeneity; Homeostasis; Immunity; Impairment; Interdisciplinary Study; Intracellular Space; Intracellular Transport; Kinetics; Lead; Malignant Neoplasms; Mammalian Cell; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Molecular; Monitor; Neurons; Nutrient; Nutrition Disorders; Obesity; Pathway interactions; Positioning Attribute; Post-Translational Protein Processing; Production; Proteins; Regulation; Research; Resources; Shapes; Signal Pathway; Tumor Cell Invasion; base; cell motility; detection of nutrient; experimental study; insight; nervous system development; programs; spatiotemporal; wound healing

Project Summary/Abstract Every cell must constantly monitor its energy level and appropriately adjust energy production rates, based on metabolic demand to maintain homeostasis. Continuous fulfillment of this energy demand depends on sufficient nutrient supply, sensing nutrient availability, metabolizing and converting into chemical energy. In eukaryotic cells energy, in the form of ATP, is mainly produced by mitochondria. Not only how much total ATP is generated, local energy level is also important for cells to carry out critical functions, such as neuronal activity, cell migration, tumor cell invasion, wound healing, and immunity. Intracellular transport and positioning of mitochondria shape spatiotemporal heterogeneity in ATP distribution. My overall goal is to understand the molecular pathways regulating the interplay between cellular metabolism, mitochondrial positioning and function. The estimated mitochondrial protein number is ~1,200 for mammalian cells. Post- translational modifications can further magnify the functional diversity of proteins. Metabolic flux- sensitive post-translational modification, O-GlcNAcylation, uniquely couple nutrient status to cellular metabolism and signaling pathways. While my research will be focused on O- GlcNAcylation-dependent regulation of mitochondrial functions, systematic analysis of metabolic enzyme functions within the intracellular space will add extra dimension to our understanding of metabolic pathways. Our experiments will decipher the metabolic biochemistry and metabolite kinetics within the context of cellular architecture. My interdisciplinary research program is poised to reveal fundamental insights into the mechanisms that orchestrate the nutrient and energy supply, and pinpoint the underlying causes of energy impairments that lead to diseases. !

项目摘要/摘要 每个电池都必须不断地监测自己的能量水平，并适当调整能量生产 利率，根据新陈代谢需求来维持动态平衡。不断地实现这一能量 需求取决于充足的养分供应，感知养分的可用性，代谢和 转化为化学能。在真核细胞中，能量以三磷酸腺苷的形式主要产生 通过线粒体。不仅产生了多少总的ATP，当地的能量水平也很重要 对于细胞执行关键功能，如神经元活动，细胞迁移，肿瘤细胞侵袭， 伤口愈合和免疫力。线粒体形状的细胞内运输和定位 ATP分布的时空异质性。我的总体目标是了解分子 调控细胞代谢、线粒体定位和细胞外信号转导相互作用的途径 功能。据估计，哺乳动物细胞的线粒体蛋白质数量约为1200个。邮寄- 翻译修饰可以进一步放大蛋白质的功能多样性。代谢流量- 敏感的翻译后修饰，O-GlcN酰化，独特地将营养状态与 细胞代谢和信号通路。虽然我的研究将集中在O- GlcN酰化依赖的线粒体功能调节，代谢的系统分析 细胞内空间内的酶功能将增加我们对 代谢途径。我们的实验将破译代谢生物化学和代谢物 蜂窝建筑背景下的动力学。我的跨学科研究项目已经准备就绪 揭示协调营养和能量的机制的基本见解 能源供应，并找出导致疾病的能源损伤的根本原因。 好了！