Stress Response Pathways

Miller, Dana L.; Horsman, Joseph W.; Heinis, Frazer I.

doi:10.1007/978-3-319-44703-2_9

Cited by 2 publications

(1 citation statement)

References 208 publications

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“…Cellular surveillance programs that detect disruption of normal cellular processes license TF activity by triggering post-translational changes, such as re-localization, phosphorylation, or proteolytic cleavage. These patterns have been repeatedly observed across biological phyla for a variety of stresses, including heat shock [1], hypoxia [2], proteostatic disruption in the ER and mitochondria [3][4][5], and many others [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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

2020

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Background 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 healthspan.

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Section: Introductionmentioning

confidence: 99%

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

2020

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The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity

et al. 2019

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Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcription elongation and splicing factor, TCERG1, has opposite effects on lifespan and stress resistance. We previously showed that tcer-1 promotes longevity in germline-less C. elegans and reproductive fitness in wild-type animals. Surprisingly, tcer-1 mutants exhibit exceptional resistance against multiple stressors, including infection by human opportunistic pathogens, whereas, TCER-1 overexpression confers immuno-susceptibility. TCER-1 inhibits immunity only during fertile stages of life. Elevating its levels ameliorates the fertility loss caused by infection, suggesting that TCER-1 represses immunity to augment fecundity. TCER-1 acts through repression of PMK-1 as well as PMK-1-independent factors critical for innate immunity. Our data establish key roles for TCER-1 in coordinating immunity, longevity and fertility, and reveal mechanisms that distinguish length of life from functional aspects of aging.

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Stress Response Pathways

Cited by 2 publications

References 208 publications

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

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

The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity

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