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The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response

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Názov: The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response
Autori: Chamseddine, Douja, Mahmud, Siraje A., Westfall, Aundrea K., Castoe, Todd A., Berg, Rance E., Pellegrino, Mark W.
Zdroj: Cell Reports
Informácie o vydavateľovi: Elsevier B.V.
Rok vydania: 2023
Zbierka: UNTHSC Scholarly Repository (University. of North Texas Health Science Center)
Predmety: Atf5, CP: Metabolism, CP: Molecular biology, UPR(mt), cholecystokinin, colitis, epithelial barrier, host-pathogen interaction, hyperglycemia, leptin, mitochondria, satiety, Animals, Caenorhabditis elegans / metabolism, Caenorhabditis elegans Proteins / genetics, Caenorhabditis elegans Proteins / metabolism, Satiety Response, Mitochondria / metabolism, Unfolded Protein Response, Mammals / metabolism
Popis: Organisms use several strategies to mitigate mitochondrial stress, including the activation of the mitochondrial unfolded protein response (UPR(mt)). The UPR(mt) 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. ; Research funds were provided by the National Institutes of Health (R35GM128885) and the Cancer Prevention & Research Institute of Texas (RR160053) to M.W.P., a CPRIT Scholar in Cancer Research.
Druh dokumentu: article in journal/newspaper
Popis súboru: application/pdf
Jazyk: unknown
Relation: https://doi.org/10.1016/j.celrep.2022.111789; Chamseddine, D., Mahmud, S. A., Westfall, A. K., Castoe, T. A., Berg, R. E., & Pellegrino, M. W. (2022). The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response. Cell reports, 41(11), 111789. https://doi.org/10.1016/j.celrep.2022.111789; https://hdl.handle.net/20.500.12503/31998; 41; 11
Dostupnosť: https://hdl.handle.net/20.500.12503/31998
Rights: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ ; © 2022 The Author(s).
Prístupové číslo: edsbas.EB99ADC2
Databáza: BASE
Popis
Abstrakt:Organisms use several strategies to mitigate mitochondrial stress, including the activation of the mitochondrial unfolded protein response (UPR(mt)). The UPR(mt) 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. ; Research funds were provided by the National Institutes of Health (R35GM128885) and the Cancer Prevention & Research Institute of Texas (RR160053) to M.W.P., a CPRIT Scholar in Cancer Research.