ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging. / Snieckute, Goda; Ryder, Laura; Vind, Anna Constance; Wu, Zhenzhen; Arendrup, Frederic Schrøder; Stoneley, Mark; Chamois, Sébastien; Martinez-Val, Ana; Leleu, Marion; Dreos, René; Russell, Alexander; Gay, David Michael; Genzor, Aitana Victoria; Choi, Beatrice So-Yun; Basse, Astrid Linde; Sass, Frederike; Dall, Morten; Dollet, Lucile Chantal Marie; Blasius, Melanie; Willis, Anne E; Lund, Anders H; Treebak, Jonas T; Olsen, Jesper Velgaard; Poulsen, Steen Seier; Pownall, Mary Elizabeth; Jensen, Benjamin Anderschou Holbech; Clemmensen, Christoffer; Gerhart-Hines, Zach; Gatfield, David; Bekker-Jensen, Simon.

In: Science (New York, N.Y.), Vol. 382, No. 6675, eadf3208, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Snieckute, G, Ryder, L, Vind, AC, Wu, Z, Arendrup, FS, Stoneley, M, Chamois, S, Martinez-Val, A, Leleu, M, Dreos, R, Russell, A, Gay, DM, Genzor, AV, Choi, BS-Y, Basse, AL, Sass, F, Dall, M, Dollet, LCM, Blasius, M, Willis, AE, Lund, AH, Treebak, JT, Olsen, JV, Poulsen, SS, Pownall, ME, Jensen, BAH, Clemmensen, C, Gerhart-Hines, Z, Gatfield, D & Bekker-Jensen, S 2023, 'ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging', Science (New York, N.Y.), vol. 382, no. 6675, eadf3208. https://doi.org/10.1126/science.adf3208

APA

Snieckute, G., Ryder, L., Vind, A. C., Wu, Z., Arendrup, F. S., Stoneley, M., Chamois, S., Martinez-Val, A., Leleu, M., Dreos, R., Russell, A., Gay, D. M., Genzor, A. V., Choi, B. S-Y., Basse, A. L., Sass, F., Dall, M., Dollet, L. C. M., Blasius, M., ... Bekker-Jensen, S. (2023). ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging. Science (New York, N.Y.), 382(6675), [eadf3208]. https://doi.org/10.1126/science.adf3208

Vancouver

Snieckute G, Ryder L, Vind AC, Wu Z, Arendrup FS, Stoneley M et al. ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging. Science (New York, N.Y.). 2023;382(6675). eadf3208. https://doi.org/10.1126/science.adf3208

Author

Snieckute, Goda ; Ryder, Laura ; Vind, Anna Constance ; Wu, Zhenzhen ; Arendrup, Frederic Schrøder ; Stoneley, Mark ; Chamois, Sébastien ; Martinez-Val, Ana ; Leleu, Marion ; Dreos, René ; Russell, Alexander ; Gay, David Michael ; Genzor, Aitana Victoria ; Choi, Beatrice So-Yun ; Basse, Astrid Linde ; Sass, Frederike ; Dall, Morten ; Dollet, Lucile Chantal Marie ; Blasius, Melanie ; Willis, Anne E ; Lund, Anders H ; Treebak, Jonas T ; Olsen, Jesper Velgaard ; Poulsen, Steen Seier ; Pownall, Mary Elizabeth ; Jensen, Benjamin Anderschou Holbech ; Clemmensen, Christoffer ; Gerhart-Hines, Zach ; Gatfield, David ; Bekker-Jensen, Simon. / ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging. In: Science (New York, N.Y.). 2023 ; Vol. 382, No. 6675.

Bibtex

@article{a300300f25e2405d858dbe89c4b8a0f8,
title = "ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging",
abstract = "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.",
keywords = "Mice, Animals, Reactive Oxygen Species/metabolism, Zebrafish, Ribosomes/metabolism, Aging, Obesity/genetics",
author = "Goda Snieckute and Laura Ryder and Vind, {Anna Constance} and Zhenzhen Wu and Arendrup, {Frederic Schr{\o}der} and Mark Stoneley and S{\'e}bastien Chamois and Ana Martinez-Val and Marion Leleu and Ren{\'e} Dreos and Alexander Russell and Gay, {David Michael} and Genzor, {Aitana Victoria} and Choi, {Beatrice So-Yun} and Basse, {Astrid Linde} and Frederike Sass and Morten Dall and Dollet, {Lucile Chantal Marie} and Melanie Blasius and Willis, {Anne E} and Lund, {Anders H} and Treebak, {Jonas T} and Olsen, {Jesper Velgaard} and Poulsen, {Steen Seier} and Pownall, {Mary Elizabeth} and Jensen, {Benjamin Anderschou Holbech} and Christoffer Clemmensen and Zach Gerhart-Hines and David Gatfield and Simon Bekker-Jensen",
year = "2023",
doi = "10.1126/science.adf3208",
language = "English",
volume = "382",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6675",

}

RIS

TY - JOUR

T1 - ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging

AU - Snieckute, Goda

AU - Ryder, Laura

AU - Vind, Anna Constance

AU - Wu, Zhenzhen

AU - Arendrup, Frederic Schrøder

AU - Stoneley, Mark

AU - Chamois, Sébastien

AU - Martinez-Val, Ana

AU - Leleu, Marion

AU - Dreos, René

AU - Russell, Alexander

AU - Gay, David Michael

AU - Genzor, Aitana Victoria

AU - Choi, Beatrice So-Yun

AU - Basse, Astrid Linde

AU - Sass, Frederike

AU - Dall, Morten

AU - Dollet, Lucile Chantal Marie

AU - Blasius, Melanie

AU - Willis, Anne E

AU - Lund, Anders H

AU - Treebak, Jonas T

AU - Olsen, Jesper Velgaard

AU - Poulsen, Steen Seier

AU - Pownall, Mary Elizabeth

AU - Jensen, Benjamin Anderschou Holbech

AU - Clemmensen, Christoffer

AU - Gerhart-Hines, Zach

AU - Gatfield, David

AU - Bekker-Jensen, Simon

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Mice

KW - Animals

KW - Reactive Oxygen Species/metabolism

KW - Zebrafish

KW - Ribosomes/metabolism

KW - Aging

KW - Obesity/genetics

U2 - 10.1126/science.adf3208

DO - 10.1126/science.adf3208

M3 - Journal article

C2 - 38060659

VL - 382

JO - Science

JF - Science

SN - 0036-8075

IS - 6675

M1 - eadf3208

ER -

ID: 376296659