Regulation of mitochondrial dynamics by the AMPK pathway

为了生存，动物需要小心地将食物摄入与能量消耗相匹配。这是通过一个复杂的通讯系统在生物体细胞之间以及每个细胞内部发生的。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，AMPK被激活，以抑制能量消耗过程，促进营养物质的吸收和再循环。细胞的大部分能量是由从细胞外输入到细胞器线粒体的营养物质产生的。这些线粒体还通过其长度和内部结构的动态变化受到营养可利用性变化的影响。事实上，线粒体是高度动态的细胞器，它不断地融合和分裂，这一过程对线粒体功能有重大影响，包括能量产生和细胞死亡的调节。虽然允许线粒体融合和分裂的机制已经确定，但调节这些变化的信号仍然知之甚少。在本提案中，我们将研究线粒体动力学对营养可用性变化的调节，重点是重要的通信枢纽AMPK。通过定义在营养可用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，这是生物体中其他一切都依赖的细胞过程。

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.