Metabolic Regulation of Mitochondrial Function

线粒体功能的代谢调节

• 批准号: 10174951
• 负责人: Gulcin Pekkurnaz
• 金额: $ 37.07万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10174951
• 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. !

项目总结/文摘