Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response.
Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3879150?pdf=render |
| _version_ | 1818544387905290240 |
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| author | Vyacheslav M Labunskyy Maxim V Gerashchenko Joe R Delaney Alaattin Kaya Brian K Kennedy Matt Kaeberlein Vadim N Gladyshev |
| author_facet | Vyacheslav M Labunskyy Maxim V Gerashchenko Joe R Delaney Alaattin Kaya Brian K Kennedy Matt Kaeberlein Vadim N Gladyshev |
| author_sort | Vyacheslav M Labunskyy |
| collection | DOAJ |
| description | Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast. This extended lifespan depends on a functional ER stress sensor protein, Ire1p, and is associated with constitutive activation of upstream UPR signaling. We applied ribosome profiling coupled with next generation sequencing to quantitatively examine translational changes associated with increased UPR activity and identified a set of stress response factors up-regulated in the long-lived mutants. Besides known UPR targets, we uncovered up-regulation of components of the cell wall and genes involved in cell wall biogenesis that confer resistance to multiple stresses. These findings demonstrate that the UPR is an important determinant of lifespan that governs ER stress and identify a signaling network that couples stress resistance to longevity. |
| first_indexed | 2024-12-11T22:47:50Z |
| format | Article |
| id | doaj.art-c0e6ead76b0846d2adf2ec34ad96ba32 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T22:47:50Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-c0e6ead76b0846d2adf2ec34ad96ba322022-12-22T00:47:34ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-01-01101e100401910.1371/journal.pgen.1004019Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response.Vyacheslav M LabunskyyMaxim V GerashchenkoJoe R DelaneyAlaattin KayaBrian K KennedyMatt KaeberleinVadim N GladyshevCells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast. This extended lifespan depends on a functional ER stress sensor protein, Ire1p, and is associated with constitutive activation of upstream UPR signaling. We applied ribosome profiling coupled with next generation sequencing to quantitatively examine translational changes associated with increased UPR activity and identified a set of stress response factors up-regulated in the long-lived mutants. Besides known UPR targets, we uncovered up-regulation of components of the cell wall and genes involved in cell wall biogenesis that confer resistance to multiple stresses. These findings demonstrate that the UPR is an important determinant of lifespan that governs ER stress and identify a signaling network that couples stress resistance to longevity.http://europepmc.org/articles/PMC3879150?pdf=render |
| spellingShingle | Vyacheslav M Labunskyy Maxim V Gerashchenko Joe R Delaney Alaattin Kaya Brian K Kennedy Matt Kaeberlein Vadim N Gladyshev Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. PLoS Genetics |
| title | Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. |
| title_full | Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. |
| title_fullStr | Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. |
| title_full_unstemmed | Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. |
| title_short | Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. |
| title_sort | lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response |
| url | http://europepmc.org/articles/PMC3879150?pdf=render |
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