Reference - Detail
| RRC ID | 88130 |
|---|---|
| Author | Zhou Y, Ahsan FM, Emans SW, Soukas AA. |
| Title | The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity. |
| Journal | Mol Cell |
| 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 central energy sensor, AMP-activated protein kinase (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 transcriptional 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 in humans, indicating that bridging energy sensing to metabolic adaptation is an ancient role of this signaling axis. |
| Volume | 85(19) |
| Pages | 3605-3622.e10 |
| Published | 2025-10-2 |
| DOI | 10.1016/j.molcel.2025.08.035 |
| PII | S1097-2765(25)00741-5 |
| PMID | 40992375 |
| MeSH | AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism Active Transport, Cell Nucleus Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Energy Metabolism* Humans Intrinsically Disordered Proteins / genetics Intrinsically Disordered Proteins / metabolism Longevity* / genetics Nuclear Pore* / genetics Nuclear Pore* / metabolism Nuclear Pore Complex Proteins* / genetics Nuclear Pore Complex Proteins* / metabolism Signal Transduction Stress, Physiological Transcription, Genetic* Transcriptional Activation |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1978 |