VRK-1 extends life span by activation of AMPK via phosphorylation
| Autor: | Murat Artan, Seung-Jae Lee, Seung Hyun Han, Sangsoon Park, Ara B. Hwang, Kyong-Tai Kim, Yoonji Jung, Wonsik Shin, Hae-Eun H. Park |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Multidisciplinary Kinase Somatic cell media_common.quotation_subject Longevity SciAdv r-articles AMPK Cell Biology Biology biology.organism_classification Cell biology 03 medical and health sciences 0302 clinical medicine Phosphorylation Nuclear protein Organismal Biology Protein kinase A Research Articles 030217 neurology & neurosurgery Caenorhabditis elegans Research Article 030304 developmental biology media_common |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | A conserved protein kinase VRK-1 increases life span by activating a key energy sensor AMPK in the roundworm C. elegans. Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between C. elegans and humans. |
| Databáze: | OpenAIRE |
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