未折叠蛋白反应
秀丽隐杆线虫
细胞生物学
势垒函数
生物
转录因子
调节器
分泌物
线粒体
内质网
生物化学
内分泌学
基因
作者
Douja Chamseddine,Siraje Arif Mahmud,Aundrea K. Westfall,Todd A. Castoe,Rance E. Berg,Mark W. Pellegrino
出处
期刊:Cell Reports
[Elsevier]
日期:2022-12-01
卷期号:41 (11): 111789-111789
被引量:1
标识
DOI:10.1016/j.celrep.2022.111789
摘要
Organisms use several strategies to mitigate mitochondrial stress, including the activation of the mitochondrial unfolded protein response (UPRmt). The UPRmt in Caenorhabditis elegans, regulated by the transcription factor ATFS-1, expands on this recovery program by inducing an antimicrobial response against pathogens that target mitochondrial function. Here, we show that the mammalian ortholog of ATFS-1, ATF5, protects the host during infection with enteric pathogens but, unexpectedly, by maintaining the integrity of the intestinal barrier. Intriguingly, ATF5 supports intestinal barrier function by promoting a satiety response that prevents obesity and associated hyperglycemia. This consequently averts dysregulated glucose metabolism that is detrimental to barrier function. Mechanistically, we show that intestinal ATF5 stimulates the satiety response by transcriptionally regulating the gastrointestinal peptide hormone cholecystokinin, which promotes the secretion of the hormone leptin. We propose that ATF5 protects the host from enteric pathogens by promoting intestinal barrier function through a satiety-response-mediated metabolic control mechanism.
科研通智能强力驱动
Strongly Powered by AbleSci AI