Regulation of mitochondrial dynamics by the AMPK pathway

AMPK 通路对线粒体动力学的调节

• 批准号: 435605-2013
• 负责人: Germain, Marc
• 金额: $ 2.33万
• 依托单位: Université du Québec à Trois-Rivières
• 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=630071
• 关键词: Regulation; mitochondrial; dynamics; AMPK; pathway

To survive, animals need to carefully match their food intake with the amount of energy they spend. This occurs through a complex communication system between the cells of the organism as well as inside each cell. One important hub of this communication system is a protein named AMPK, which is activated when cellular energy levels drop to inhibit energy consuming processes and promote nutrient uptake and recycling. Most of the cellular energy is made from nutrients imported from outside of the cell into an organelle called mitochondria. These mitochondria are also affected by changes in nutrient availability through dynamic changes in their length and internal structure. Indeed, mitochondria are highly dynamic organelles that constantly fuse together and divide, a process that has a major impact on mitochondrial function, including energy production and the regulation of cell death. While the mechanisms allowing mitochondria to fuse and divide have been defined, the signals regulating these changes are still poorly understood. In this proposal, we will examine the regulation of mitochondrial dynamics upon changes in nutrient availability, with an emphasis on the important communication hub that is AMPK. By defining the signals regulating mitochondrial dynamics upon changes in nutrient availability, we will better understand the control of metabolic regulation, a cellular process on which everything else in the organism depends.

为了生存，动物需要仔细地将它们的食物摄入量与它们消耗的能量相匹配。这通过生物体细胞之间以及每个细胞内部的复杂通信系统发生。这个通讯系统的一个重要枢纽是一种名为AMPK的蛋白质，当细胞能量水平下降时，它会被激活，以抑制能量消耗过程，促进营养吸收和循环。大部分细胞能量是由从细胞外输入到称为线粒体的细胞器的营养物质构成的。这些线粒体还通过其长度和内部结构的动态变化而受到营养可获得性变化的影响。事实上，线粒体是高度动态的细胞器，不断地融合和分裂，这一过程对线粒体的功能有重大影响，包括能量产生和细胞死亡的调节。虽然线粒体融合和分裂的机制已经确定，但调控这些变化的信号仍然知之甚少。在这项提案中，我们将研究线粒体动力学对营养可获得性变化的调节，重点是重要的通讯枢纽AMPK。通过定义在营养可获得性变化时调节线粒体动力学的信号，我们将更好地理解代谢调节的控制，这是有机体中其他一切都依赖的细胞过程。