دورية أكاديمية
ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging.
| العنوان: | ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging. |
|---|---|
| المؤلفون: | Snieckute G; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Ryder L; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Vind AC; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Wu Z; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Arendrup FS; Biotech Research and Innovation Center, University of Copenhagen, DK-2200 Copenhagen, Denmark., Stoneley M; MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK., Chamois S; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Martinez-Val A; Mass Spectrometry for Quantitative Proteomics, Proteomics Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark., Leleu M; Bioinformatics Competence Center, Ecole Polytechnique Fédérale de Lausanne and University of Lausanne, CH-1015 Lausanne, Switzerland., Dreos R; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Russell A; Department of Biology, University of York, York YO10 5DD, UK., Gay DM; Biotech Research and Innovation Center, University of Copenhagen, DK-2200 Copenhagen, Denmark., Genzor AV; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Choi BS; Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Basse AL; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Sass F; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Dall M; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Dollet LCM; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Blasius M; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark., Willis AE; MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK., Lund AH; Biotech Research and Innovation Center, University of Copenhagen, DK-2200 Copenhagen, Denmark., Treebak JT; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Olsen JV; Mass Spectrometry for Quantitative Proteomics, Proteomics Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark., Poulsen SS; Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Pownall ME; Department of Biology, University of York, York YO10 5DD, UK., Jensen BAH; Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Clemmensen C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Gerhart-Hines Z; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Gatfield D; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Bekker-Jensen S; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark. |
| المصدر: | Science (New York, N.Y.) [Science] 2023 Dec 08; Vol. 382 (6675), pp. eadf3208. Date of Electronic Publication: 2023 Dec 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Aging*/metabolism , MAP Kinase Kinase Kinase 3*/genetics , MAP Kinase Kinase Kinase 3*/metabolism , Obesity*/metabolism , Reactive Oxygen Species*/metabolism , Ribosomes*/metabolism , Stress, Physiological*, Animals ; Mice ; Protein Biosynthesis ; Zebrafish ; Mice, Knockout |
| مستخلص: | The ribotoxic stress response (RSR) is a signaling pathway in which the p38- and c-Jun N-terminal kinase (JNK)-activating mitogen-activated protein kinase kinase kinase (MAP3K) ZAKα senses stalling and/or collision of ribosomes. Here, we show that reactive oxygen species (ROS)-generating agents trigger ribosomal impairment and ZAKα activation. Conversely, zebrafish larvae deficient for ZAKα are protected from ROS-induced pathology. Livers of mice fed a ROS-generating diet exhibit ZAKα-activating changes in ribosomal elongation dynamics. Highlighting a role for the RSR in metabolic regulation, ZAK-knockout mice are protected from developing high-fat high-sugar (HFHS) diet-induced blood glucose intolerance and liver steatosis. Finally, ZAK ablation slows animals from developing the hallmarks of metabolic aging. Our work highlights ROS-induced ribosomal impairment as a physiological activation signal for ZAKα that underlies metabolic adaptation in obesity and aging. |
| معلومات مُعتمدة: | MC_UU_00025/7 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | EC 2.7.11.25 (MAP Kinase Kinase Kinase 3) 0 (Reactive Oxygen Species) |
| تواريخ الأحداث: | Date Created: 20231207 Date Completed: 20231221 Latest Revision: 20240306 |
| رمز التحديث: | 20240306 |
| DOI: | 10.1126/science.adf3208 |
| PMID: | 38060659 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-9203 |
|---|---|
| DOI: | 10.1126/science.adf3208 |