脂肪酸合酶
下调和上调
蛋白质水解
秀丽隐杆线虫
细胞生物学
生物
化学
脂肪酸
生物化学
酶
基因
作者
Hai Wei,Yi M. Weaver,Chendong Yang,Yuan Zhang,Guoli Hu,Courtney M. Karner,Matthew Sieber,Ralph J. DeBerardinis,Benjamin P. Weaver
标识
DOI:10.1038/s42255-023-00939-z
摘要
Abstract Chronic stress and inflammation are both outcomes and major drivers of many human diseases. Sustained responsiveness despite mitigation suggests a failure to sense resolution of the stressor. Here we show that a proteolytic cleavage event of fatty acid synthase (FASN) activates a global cue for stress resolution in Caenorhabditis elegans . FASN is well established for biosynthesis of the fatty acid palmitate. Our results demonstrate FASN promoting an anti-inflammatory profile apart from palmitate synthesis. Redox-dependent proteolysis of limited amounts of FASN by caspase activates a C-terminal fragment sufficient to downregulate multiple aspects of stress responsiveness, including gene expression, metabolic programs and lipid droplets. The FASN C-terminal fragment signals stress resolution in a cell non-autonomous manner. Consistent with these findings, FASN processing is also seen in well-fed but not fasted male mouse liver. As downregulation of stress responses is critical to health, our findings provide a potential pathway to control diverse aspects of stress responses.
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