翻译(生物学)
细胞生物学
生物
代谢途径
信号转导
战斗或逃跑反应
综合应力响应
信号通路
计算生物学
化学
生物信息学
生物化学
遗传学
新陈代谢
信使核糖核酸
基因
作者
Goda Snieckute,Aitana Victoria Genzor,Anna 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
出处
期刊:Cell Metabolism
[Cell Press]
日期:2022-11-15
卷期号:34 (12): 2036-2046.e8
被引量:93
标识
DOI:10.1016/j.cmet.2022.10.011
摘要
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.
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