scholarly journals The integrated stress response in budding yeast lifespan extension

2017 ◽  
Vol 4 (11) ◽  
pp. 368-375 ◽  
Author(s):  
Spike D.L. Postnikoff ◽  
Jay E. Johnson ◽  
Jessica K. Tyler
Keyword(s):  
Stress Response ◽  
Budding Yeast ◽  
Lifespan Extension ◽  
Integrated Stress Response

scholarly journals Mutagenesis screen uncovers lifespan extension through integrated stress response inhibition without reduced mRNA translation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maxime J. Derisbourg ◽  
Laura E. Wester ◽  
Ruth Baddi ◽  
Martin S. Denzel
Keyword(s):  
Stress Response ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Lifespan Extension ◽  
Protein Homeostasis ◽  
Integrated Stress Response ◽  
Mutagenesis Screen

AbstractProtein homeostasis is modulated by stress response pathways and its deficiency is a hallmark of aging. The integrated stress response (ISR) is a conserved stress-signaling pathway that tunes mRNA translation via phosphorylation of the translation initiation factor eIF2. ISR activation and translation initiation are finely balanced by eIF2 kinases and by the eIF2 guanine nucleotide exchange factor eIF2B. However, the role of the ISR during aging remains poorly understood. Using a genomic mutagenesis screen for longevity inCaenorhabditis elegans, we define a role of eIF2 modulation in aging. By inhibiting the ISR, dominant mutations in eIF2B enhance protein homeostasis and increase lifespan. Consistently, full ISR inhibition using phosphorylation-defective eIF2α or pharmacological ISR inhibition prolong lifespan. Lifespan extension through impeding the ISR occurs without a reduction in overall protein synthesis. Instead, we observe changes in the translational efficiency of a subset of mRNAs, of which the putative kinasekin-35is required for lifespan extension. Evidently, lifespan is limited by the ISR and its inhibition may provide an intervention in aging.

scholarly journals Integrated Stress Response Inhibitor Reverses Sex-Dependent Behavioral and Cell-Specific Deficits after Mild Repetitive Head Trauma

2020 ◽  
Vol 37 (11) ◽  
pp. 1370-1380 ◽  
Author(s):  
Karen Krukowski ◽  
Amber Nolan ◽  
Elma S. Frias ◽  
Katherine Grue ◽  
McKenna Becker ◽  
...  
Keyword(s):  
Stress Response ◽  
Head Trauma ◽  
Integrated Stress Response

scholarly journals Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai-Ling Tian ◽  
Qi Wu ◽  
Peng Liu ◽  
Liwei Zhao ◽  
Isabelle Martins ◽  
...  
Keyword(s):  
Stress Response ◽  
Immune Responses ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Serine Residue ◽  
Eif2α Phosphorylation ◽  
Lysosomotropic Agents ◽  
Cultured Human Cells

AbstractThe integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

scholarly journals Targeting the integrated stress response in ophthalmology

2021 ◽  
pp. 1-14
Author(s):  
Hsiao-Sang Chu ◽  
Cornelia Peterson ◽  
Albert Jun ◽  
James Foster
Keyword(s):  
Stress Response ◽  
Integrated Stress Response
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