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bioRxiv · 10.1101/2025.02.17.638704

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

Zhou, Y.·Ahsan, F.·Soukas, A. A.
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Abstract

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.

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Zhou, Y., Ahsan, F., Soukas, A. A.. 2025-02-17. The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity. https://doi.org/10.1101/2025.02.17.638704

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