The evolutionarily conserved ESRE stress response network is activated by ROS and mitochondrial damage

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dc.citation.articleNumber74en_US
dc.citation.journalTitleBMC Biologyen_US
dc.citation.volumeNumber18en_US
dc.contributor.authorTjahjono, Elissaen_US
dc.contributor.authorMcAnena, Aidan P.en_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.date.accessioned2020-10-16T18:17:13Zen_US
dc.date.available2020-10-16T18:17:13Zen_US
dc.date.issued2020en_US
dc.description.abstractBackground: Mitochondrial dysfunction causes or contributes to a wide variety of pathologies, including neurodegenerative diseases, cancer, metabolic diseases, and aging. Cells actively surveil a number of mitochondrial readouts to ensure that cellular homeostasis is maintained. Results: In this article, we characterize the role of the ethanol and stress response element (ESRE) pathway in mitochondrial surveillance and show that it is robustly activated when the concentration of reactive oxygen species (ROS) in the cell increases. While experiments were mostly performed in Caenorhabditis elegans, we observed similar gene activation profile in human cell lines. The linear relationship between ROS and ESRE activation differentiates ESRE from known mitochondrial surveillance pathways, such as the mitochondrial unfolded protein response (UPRmt), which monitor mitochondrial protein import. The ability of the ESRE network to be activated by increased ROS allows the cell to respond to oxidative and reductive stresses. The ESRE network works in tandem with other mitochondrial surveillance mechanisms as well, in a fashion that suggests a partially redundant hierarchy. For example, mutation of the UPRmt pathway results in earlier and more robust activation of the ESRE pathway. Interestingly, full expression of ATFS-1, a key transcription factor for the UPRmt, requires the presence of an ESRE motif in its promoter region. Conclusion: The ESRE pathway responds to mitochondrial damage by monitoring ROS levels. This response is conserved in humans. The ESRE pathway is activated earlier when other mitochondrial surveillance pathways are unavailable during mitochondrial crises, potentially to mitigate stress and restore health. However, the exact mechanisms of pathway activation and crosstalk remain to be elucidated. Ultimately, a better understanding of this network, and its role in the constellation of mitochondrial and cellular stress networks, will improve healthspanen_US
dc.identifier.citationTjahjono, Elissa, McAnena, Aidan P. and Kirienko, Natalia V.. "The evolutionarily conserved ESRE stress response network is activated by ROS and mitochondrial damage." <i>BMC Biology,</i> 18, (2020) Springer Nature: https://doi.org/10.1186/s12915-020-00812-5.en_US
dc.identifier.doihttps://doi.org/10.1186/s12915-020-00812-5en_US
dc.identifier.urihttps://hdl.handle.net/1911/109425en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe evolutionarily conserved ESRE stress response network is activated by ROS and mitochondrial damageen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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