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

Autor:	Goda Snieckute, Aitana Victoria Genzor, Anna Constance Vind, Laura Ryder, Mark Stoneley, Sébastien Chamois, René Dreos, Cathrine Nordgaard, Frederike Sass, Melanie Blasius, Aida Rodríguez López, Sólveig Hlín Brynjólfsdóttir, Kasper Langebjerg Andersen, Anne E. Willis, Lisa B. Frankel, Steen Seier Poulsen, David Gatfield, Zachary Gerhart-Hines, Christoffer Clemmensen, Simon Bekker-Jensen
Rok vydání:	2022
Předmět:	amino acid starvation AMPK Animals Male Mice Ribosomes MAP Kinase Kinase Kinases/metabolism Protein Biosynthesis Stress Physiological FGF21 ZAK-alpha mTOR metabolic regulation mouse models ribosome collision ribotoxic stress response Physiology Cell Biology Molecular Biology
Zdroj:	Cell Metabolism Cell metabolism, vol. 34, no. 12, pp. 2036-2046.e8 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, vol. 34, no. 12, pp. 2036-2046.e8 . https://doi.org/10.1016/j.cmet.2022.10.011
ISSN:	1550-4131
DOI:	10.1016/j.cmet.2022.10.011
Popis:	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.
Databáze:	OpenAIRE
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