Drosophila energetics and mito-nuclear function

果蝇能量学和线粒体核功能

• 批准号: 7052535
• 负责人: KRISTI L MONTOOTH
• 金额: $ 4.6万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052535
• 关键词: Drosophilidae; arthropod genetics; bioenergetics; biological models; caloric dietary content; cell nucleus; dietary control; genetic regulation; genetically modified animals; glycolysis; messenger RNA; mitochondria; mitochondrial DNA; molecular genetics; nutrition related tag; oxidative phosphorylation; postdoctoral investigator

DESCRIPTION (provided by applicant): Proper energy allocation underlies metabolic health and requires the evolved cooperation of the mitochondrial and nuclear genomes, embedded in a context of diet. Human metabolic disease is increasingly viewed in the framework of energy homeostasis. Because energetic processes are highly conserved, this study of Drosophila addresses key issues for understanding human metabolic disease - the physiological consequences of mitochondrial-nuclear interactions and the role that diet plays in mediating energy metabolism. This project tests hypotheses regarding genetic relationships between energetic biochemical pathways, energy storage, metabolic rate and performance phenotypes 1) in healthy Drosophila, 2) in Drosophila with disrupted mito-nuclear genomes and 3) under normal and calorie- restricted diets. Mito-nuclear disruptions will be created by introgressing mtDNA from D. simulans into a D. melanogaster nuclear background. We will also quantify mRNA expression levels of regulatory genes involved in communication between genomes. The results will identify candidate enzyme-encoding and regulatory genes that can be further investigated for functional roles in maintaining metabolic health.

描述（由申请人提供）：适当的能量分配是代谢健康的基础，需要嵌入饮食环境中的线粒体和核基因组的进化合作。人们越来越多地在能量稳态的框架中看待人类代谢疾病。由于能量过程高度保守，这项对果蝇的研究解决了理解人类代谢疾病的关键问题——线粒体-核相互作用的生理后果以及饮食在介导能量代谢中的作用。该项目测试有关能量生化途径、能量储存、代谢率和性能表型之间遗传关系的假设：1) 健康果蝇，2) 线粒体核基因组破坏的果蝇，3) 正常和热量限制饮食下的果蝇。通过将拟果蝇的 mtDNA 渗入黑腹果蝇核背景中，可产生线粒体核破坏。我们还将量化参与基因组之间通讯的调节基因的 mRNA 表达水平。结果将确定候选酶编码和调节基因，可以进一步研究它们在维持代谢健康中的功能作用。