論文 - 詳細
| RRC ID | 76064 |
|---|---|
| 著者 | Soo SK, Traa A, Rudich PD, Mistry M, Van Raamsdonk JM. |
| タイトル | Activation of mitochondrial unfolded protein response protects against multiple exogenous stressors. |
| ジャーナル | Life Sci Alliance |
| Abstract |
The mitochondrial unfolded protein response (mitoUPR) is an evolutionarily conserved pathway that responds to mitochondria insults through transcriptional changes, mediated by the transcription factor ATFS-1/ATF-5, which acts to restore mitochondrial homeostasis. In this work, we characterized the role of ATFS-1 in responding to organismal stress. We found that activation of ATFS-1 is sufficient to cause up-regulation of genes involved in multiple stress response pathways including the DAF-16-mediated stress response pathway, the cytosolic unfolded protein response, the endoplasmic reticulum unfolded protein response, the SKN-1-mediated oxidative stress response pathway, the HIF-1-mediated hypoxia response pathway, the p38-mediated innate immune response pathway, and antioxidant genes. Constitutive activation of ATFS-1 increases resistance to multiple acute exogenous stressors, whereas disruption of atfs-1 decreases stress resistance. Although ATFS-1-dependent genes are up-regulated in multiple long-lived mutants, constitutive activation of ATFS-1 decreases lifespan in wild-type animals. Overall, our work demonstrates that ATFS-1 serves a vital role in organismal survival of acute stressors through its ability to activate multiple stress response pathways but that chronic ATFS-1 activation is detrimental for longevity. |
| 巻・号 | 4(12) |
| 公開日 | 2021-12-1 |
| DOI | 10.26508/lsa.202101182 |
| PII | 4/12/e202101182 |
| PMID | 34583931 |
| PMC | PMC8500221 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / genetics* Caenorhabditis elegans / immunology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cytosol / metabolism Endoplasmic Reticulum / metabolism Forkhead Transcription Factors / metabolism Immunity, Innate Longevity / genetics Mitochondria / metabolism* Mutation Oxidative Stress / genetics Signal Transduction / genetics* Signal Transduction / immunology Stress, Physiological / genetics* Stress, Physiological / immunology Transcription Factors / genetics Transcription Factors / metabolism* Unfolded Protein Response / genetics* Up-Regulation / genetics |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 29 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4919 |