Metabolic flexibility during challenging environmental conditions in Drosophila

果蝇在挑战性环境条件下的代谢灵活性

• 批准号: RGPIN-2017-05100
• 负责人: Pichaud, Nicolas
• 金额: $ 2.19万
• 依托单位: Université de Moncton
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630625
• 关键词: Metabolic; flexibility; during; challenging; environmental

A change in dietary resources is an important environmental parameter that can be a major force driving molecular, metabolic and physiological aspects of phenotype, and adjustments to restore cellular homeostasis are hence fundamental for the survival of organisms. The mitochondria are central to these adjustments as they integrate multiple pathways and perform one of life's most important biological functions, the ATP production. Specifically, the nutrients in the diet are processed by the cell and the resulting substrates are transported inside the mitochondria by rate-limiting carriers such as the carnitine shuttle transporting the fatty acids and the mitochondrial pyruvate carrier which transports pyruvate, the end product of glycolysis. In the mitochondria, the substrates are oxidized to provide electrons to the electron transport system (ETS), allowing the production of ATP via the oxidative phosphorylation process. The ETS is constituted of several well-known enzymatic complexes (complexes I to V), but also of other less investigated electron feeders such as the glycerol-3-phosphate shuttle and the electron transferring flavoprotein. During nutrient stress, signaling pathways involving several effectors such as the target of rapamycin, AMPK, Sirtuin-1 and insulin, have been shown to activate and modulate the mitochondrial metabolism. Another stress response, the mitochondrial unfolded protein response, can also be triggered by mild mitochondrial dysfunctions that might result from nutrient stress. However, how the cell activates these different molecular responses depending on the type and intensity of stress, to which extent these responses interact to fine-tune the mitochondrial metabolism, what ETS components are prime targets for adjustments during environmental challenges, and what are the consequences of these cellular adjustments at the phenotypic level are fundamentally important, yet largely unresolved questions.

饮食资源的变化是一个重要的环境参数，它可能是驱动表型的分子，代谢和生理方面的主要力量，因此调整以恢复细胞稳态是生物生存的基础。线粒体在整合多种途径并执行生命最重要的生物学功能之一，即ATP生产时，是这些调整的核心。具体而言，饮食中的养分是由细胞处理的，所得的底物通过限制载载载来在线粒体内运输，例如运输脂肪酸和线粒体丙酮酸载体的肉碱班车，该载酸盐载体运输了丙酮酸，该载酸酯是丙酮酸的最终产物。在线粒体中，将底物氧化以向电子传输系统（ETS）提供电子，从而通过氧化磷酸化过程产生ATP。 ETS由几种众所周知的酶复合物（络合物I至V）组成，也由其他未研究的电子馈线（如甘油-3-磷酸班乘乘坐）和电子转移黄蛋蛋白组成。在营养应激期间，已证明涉及多个效应子的信号通路，例如雷帕霉素，AMPK，SIRTUIN-1和胰岛素的靶标可以激活和调节线粒体代谢。另一种压力反应，即线粒体展开的蛋白质反应，也可以由可能由营养应激引起的轻度线粒体功能障碍触发。但是，该细胞如何根据压力的类型和强度激活这些不同的分子反应，这些响应在微分方面相互作用，以调整线粒体代谢，哪些ETS组件是环境挑战期间调整的主要目标，以及这些在表型水平上这些细胞调整的后果是什么是基本重要的，但在基本上重要，却具有重要的问题。