دورية أكاديمية
Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment
| العنوان: | Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment |
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| المؤلفون: | Chiara Rossi, Anna Fernàndez, Pascual Torres, Omar Ramirez-Nuñez, Ana Belén Granado-Serrano, Laia Fontdevila, Mònica Povedano, Reinald Pamplona, Isidro Ferrer, Manuel Portero-Otin |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 16, p 8853 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | TDP-43, Jun, REST, ERK, mitochondria, cell stress, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/22/16/8853Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms22168853 |
| الوصول الحر: | https://doaj.org/article/b90f9e6eebfa4e61bed124b6f1e5717cTest |
| رقم الانضمام: | edsdoj.b90f9e6eebfa4e61bed124b6f1e5717c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms22168853 |