Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response

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

Standard

Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response. / Snieckute, Goda; Genzor, Aitana Victoria; Vind, Anna Constance; Ryder, Laura; Stoneley, Mark; Chamois, Sébastien; Dreos, René; Nordgaard, Cathrine; Sass, Frederike; Blasius, Melanie; López, Aida Rodríguez; Brynjólfsdóttir, Sólveig Hlín; Andersen, Kasper Langebjerg; Willis, Anne E.; Frankel, Lisa B.; Poulsen, Steen Seier; Gatfield, David; Gerhart-Hines, Zachary; Clemmensen, Christoffer; Bekker-Jensen, Simon.

In: Cell Metabolism, Vol. 34, No. 12, 2022, p. 2036-2046.e8.

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

Harvard

Snieckute, G, Genzor, AV, Vind, AC, Ryder, L, Stoneley, M, Chamois, S, Dreos, R, Nordgaard, C, Sass, F, Blasius, M, López, AR, Brynjólfsdóttir, SH, Andersen, KL, Willis, AE, Frankel, LB, Poulsen, SS, Gatfield, D, Gerhart-Hines, Z, Clemmensen, C & Bekker-Jensen, S 2022, 'Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response', Cell Metabolism, vol. 34, no. 12, pp. 2036-2046.e8. https://doi.org/10.1016/j.cmet.2022.10.011

APA

Snieckute, G., Genzor, A. V., Vind, A. C., Ryder, L., Stoneley, M., Chamois, S., Dreos, R., Nordgaard, C., Sass, F., Blasius, M., López, A. R., Brynjólfsdóttir, S. H., Andersen, K. L., Willis, A. E., Frankel, L. B., Poulsen, S. S., Gatfield, D., Gerhart-Hines, Z., Clemmensen, C., & Bekker-Jensen, S. (2022). Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response. Cell Metabolism, 34(12), 2036-2046.e8. https://doi.org/10.1016/j.cmet.2022.10.011

Vancouver

Snieckute G, Genzor AV, Vind AC, Ryder L, Stoneley M, Chamois S et al. Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response. Cell Metabolism. 2022;34(12):2036-2046.e8. https://doi.org/10.1016/j.cmet.2022.10.011

Author

Snieckute, Goda ; Genzor, Aitana Victoria ; Vind, Anna Constance ; Ryder, Laura ; Stoneley, Mark ; Chamois, Sébastien ; Dreos, René ; Nordgaard, Cathrine ; Sass, Frederike ; Blasius, Melanie ; López, Aida Rodríguez ; Brynjólfsdóttir, Sólveig Hlín ; Andersen, Kasper Langebjerg ; Willis, Anne E. ; Frankel, Lisa B. ; Poulsen, Steen Seier ; Gatfield, David ; Gerhart-Hines, Zachary ; Clemmensen, Christoffer ; Bekker-Jensen, Simon. / Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response. In: Cell Metabolism. 2022 ; Vol. 34, No. 12. pp. 2036-2046.e8.

Bibtex

@article{43a2e27f90e042a88b5593c3424b76b8,

title = "Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response",

abstract = "Impairment of translation can lead to collisions of ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where ribosomal sensing by the MAP3K ZAKα leads to activation of p38 and JNK kinases. Despite these insights, the physiological ramifications of ribosomal impairment and downstream RSR signaling remain elusive. Here, we show that stalling of ribosomes is sufficient to activate ZAKα. In response to amino acid deprivation and full nutrient starvation, RSR impacts on the ensuing metabolic responses in cells, nematodes, and mice. The RSR-regulated responses in these model systems include regulation of AMPK and mTOR signaling, survival under starvation conditions, stress hormone production, and regulation of blood sugar control. In addition, ZAK−/− male mice present a lean phenotype. Our work highlights impaired ribosomes as metabolic signals and demonstrates a role for RSR signaling in metabolic regulation.",

keywords = "amino acid starvation, AMPK, FGF21, metabolic regulation, mouse models, mTOR, ribosome collision, ribotoxic stress response, ZAK-alpha",

author = "Goda Snieckute and Genzor, {Aitana Victoria} and Vind, {Anna Constance} and Laura Ryder and Mark Stoneley and S{\'e}bastien Chamois and Ren{\'e} Dreos and Cathrine Nordgaard and Frederike Sass and Melanie Blasius and L{\'o}pez, {Aida Rodr{\'i}guez} and Brynj{\'o}lfsd{\'o}ttir, {S{\'o}lveig Hl{\'i}n} and Andersen, {Kasper Langebjerg} and Willis, {Anne E.} and Frankel, {Lisa B.} and Poulsen, {Steen Seier} and David Gatfield and Zachary Gerhart-Hines and Christoffer Clemmensen and Simon Bekker-Jensen",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

doi = "10.1016/j.cmet.2022.10.011",

language = "English",

volume = "34",

pages = "2036--2046.e8",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "12",

}

RIS

TY - JOUR

T1 - Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response

AU - Snieckute, Goda

AU - Genzor, Aitana Victoria

AU - Vind, Anna Constance

AU - Ryder, Laura

AU - Stoneley, Mark

AU - Chamois, Sébastien

AU - Dreos, René

AU - Nordgaard, Cathrine

AU - Sass, Frederike

AU - Blasius, Melanie

AU - López, Aida Rodríguez

AU - Brynjólfsdóttir, Sólveig Hlín

AU - Andersen, Kasper Langebjerg

AU - Willis, Anne E.

AU - Frankel, Lisa B.

AU - Poulsen, Steen Seier

AU - Gatfield, David

AU - Gerhart-Hines, Zachary

AU - Clemmensen, Christoffer

AU - Bekker-Jensen, Simon

PY - 2022

Y1 - 2022

N2 - Impairment of translation can lead to collisions of ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where ribosomal sensing by the MAP3K ZAKα leads to activation of p38 and JNK kinases. Despite these insights, the physiological ramifications of ribosomal impairment and downstream RSR signaling remain elusive. Here, we show that stalling of ribosomes is sufficient to activate ZAKα. In response to amino acid deprivation and full nutrient starvation, RSR impacts on the ensuing metabolic responses in cells, nematodes, and mice. The RSR-regulated responses in these model systems include regulation of AMPK and mTOR signaling, survival under starvation conditions, stress hormone production, and regulation of blood sugar control. In addition, ZAK−/− male mice present a lean phenotype. Our work highlights impaired ribosomes as metabolic signals and demonstrates a role for RSR signaling in metabolic regulation.

AB - Impairment of translation can lead to collisions of ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where ribosomal sensing by the MAP3K ZAKα leads to activation of p38 and JNK kinases. Despite these insights, the physiological ramifications of ribosomal impairment and downstream RSR signaling remain elusive. Here, we show that stalling of ribosomes is sufficient to activate ZAKα. In response to amino acid deprivation and full nutrient starvation, RSR impacts on the ensuing metabolic responses in cells, nematodes, and mice. The RSR-regulated responses in these model systems include regulation of AMPK and mTOR signaling, survival under starvation conditions, stress hormone production, and regulation of blood sugar control. In addition, ZAK−/− male mice present a lean phenotype. Our work highlights impaired ribosomes as metabolic signals and demonstrates a role for RSR signaling in metabolic regulation.

KW - amino acid starvation

KW - AMPK

KW - FGF21

KW - metabolic regulation

KW - mouse models

KW - mTOR

KW - ribosome collision

KW - ribotoxic stress response

KW - ZAK-alpha

U2 - 10.1016/j.cmet.2022.10.011

DO - 10.1016/j.cmet.2022.10.011

M3 - Journal article

C2 - 36384144

AN - SCOPUS:85143642349

VL - 34

SP - 2036-2046.e8

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 12

ER -

ID: 329742165

Department of Biology