The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity

As the only gateway governing nucleocytoplasmic transport, the nuclear pore complex (NPC) maintains fundamental cellular processes and deteriorates with age. However, the study of age-related roles of single NPC components remains challenging owing to the complexity of NPC composition. Here we demonstrate that the master energy sensor, AMPK, post-translationally regulates the abundance of the nucleoporin NPP-16/NUP50 in response to nutrient availability and energetic stress. In turn, NPP-16/NUP50 promotes transcriptomic activation of lipid catabolism to extend the lifespan of Caenorhabditis elegans independently of its role in nuclear transport. Rather, the intrinsically disordered region (IDR) of NPP-16/NUP50, through direct interaction with the transcriptional machinery, transactivates the promoters of catabolic genes. Remarkably, elevated NPP-16/NUP50 levels are sufficient to promote longevity and metabolic stress defenses. AMPK-NUP50 signaling is conserved to human, indicating that bridging energy sensing to metabolic adaptation is an ancient role of this signaling axis.
The datasets contain all the unprocessed and uncompressed imaging data from this research.

作为调控核质运输的唯一门户，核孔复合物（nuclear pore complex, NPC）维系着细胞的核心生命过程，并会随衰老发生退变。然而，由于NPC组成的复杂性，针对单个NPC组分的衰老相关功能研究仍颇具挑战。本研究证实，核心能量感受器AMPK（腺苷酸活化蛋白激酶）可响应营养可利用度与能量应激，通过翻译后修饰调控核孔蛋白NPP-16/NUP50的丰度。反过来，NPP-16/NUP50能够独立于其核运输功能，促进脂质分解代谢的转录组激活，从而延长秀丽隐杆线虫（Caenorhabditis elegans）的寿命。其机制并非依赖核运输功能，而是NPP-16/NUP50的内在无序区域（intrinsically disordered region, IDR）通过与转录机器直接相互作用，反式激活分解代谢基因的启动子。值得注意的是，提升NPP-16/NUP50的表达水平足以促进长寿与代谢应激防御。AMPK-NUP50信号通路在人类中具有保守性，这表明将能量感知与代谢适应相连接是该信号轴的古老功能。
本数据集包含本研究中所有未经处理与未压缩的成像原始数据。