scholarly journals Heterogeneity in heat shock response dynamics caused by translation fidelity decline and proteostasis collapse

2019 ◽  
Author(s):  
Nadia Vertti-Quintero ◽  
Simon Berger ◽  
Xavier Casadevall i Solvas ◽  
Cyril Statzer ◽  
Jillian Annis ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Early Adulthood ◽  
Surrogate Marker ◽  
Protein Translation ◽  
Single Individual ◽  
Response Dynamics ◽  
C Elegans ◽  
Translation Fidelity ◽  
Shock Response

AbstractGenetics, environment, and stochasticity influence the rate of ageing in living organisms. Individual Caenorhabditis elegans that are genetically identical and cultured in the same environment have different lifespans, suggesting a significant role of stochasticity in ageing. We have developed a novel microfluidic methodology to measure heat-shock response as a surrogate marker for heterogeneity associated with lifespan and have quantified the heat-shock response of C. elegans at the population, single individual, and tissue levels. We have further mathematically modelled our data to identify the major drivers determining such heterogeneity. This approach demonstrates that protein translation and degradation rate constants explain the individuality of the heat-shock time-course dynamic. We observed a decline of protein turnover capacity in early adulthood, co-incidentally occurring as the predicted proteostasis collapse. We identified a decline of intestinal response as the tissue that underlies the individual heterogeneity. Additionally, we verified that individuals with enhanced translation fidelity in early adulthood live longer. Altogether, our results reveal that the stochastic onset of proteostasis collapse of somatic tissues during early adulthood reflects individual protein translation capacity underlying heterogenic ageing of isogenic C. elegans.

scholarly journals Neuronal Serotonin Release Triggers the Heat Shock Response in C. elegans in the Absence of Temperature Increase

2015 ◽  
Vol 25 (2) ◽  
pp. 163-174 ◽  
Author(s):  
Marcus C. Tatum ◽  
Felicia K. Ooi ◽  
Madhusudana Rao Chikka ◽  
Laetitia Chauve ◽  
Luis A. Martinez-Velazquez ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Temperature Increase ◽  
Serotonin Release ◽  
C Elegans ◽  
Shock Response

scholarly journals Altered proteostasis in aging and heat shock response in C. elegans revealed by analysis of the global and de novo synthesized proteome

2014 ◽  
Vol 71 (17) ◽  
pp. 3339-3361 ◽  
Author(s):  
Vanessa Liang ◽  
Milena Ullrich ◽  
Hong Lam ◽  
Yee Lian Chew ◽  
Samuel Banister ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Ribosomal Proteins ◽  
Aging Process ◽  
De Novo ◽  
Tricarboxylic Acid Cycle ◽  
Mitochondrial Enzymes ◽  
C Elegans ◽  
Shock Response

Abstract Protein misfolding and aggregation as a consequence of impaired protein homeostasis (proteostasis) not only characterizes numerous age-related diseases but also the aging process itself. Functionally related to the aging process are, among others, ribosomal proteins, suggesting an intimate link between proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in C. elegans how the proteome changes with age and in response to heat shock. Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged animals, supporting the notion that proteostasis is altered during aging. Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport chain were also reduced, consistent with an age-associated energy impairment. Moreover, we observed an age-associated decline in the heat shock response. In order to determine how protein synthesis is altered in aging and in response to heat shock, we complemented our global analysis by determining the de novo proteome. For that, we established a novel method that enables both the visualization and identification of de novo synthesized proteins, by incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into the nascent polypeptides, followed by reacting the azide group of AHA by ‘click chemistry’ with an alkyne-labeled tag. Our analysis of AHA-tagged peptides demonstrated that the decreased abundance of, for example, ribosomal proteins in aged animals is not solely due to degradation but also reflects a relative decrease in their synthesis. Interestingly, although the net rate of protein synthesis is reduced in aged animals, our analyses indicate that the synthesis of certain proteins such as the vitellogenins increases with age.

scholarly journals Stochastic and Age‐Dependent Proteostasis Decline Underlies Heterogeneity in Heat‐Shock Response Dynamics

Small ◽  
2021 ◽  
pp. 2102145
Author(s):  
Nadia Vertti‐Quintero ◽  
Simon Berger ◽  
Xavier Casadevall i Solvas ◽  
Cyril Statzer ◽  
Jillian Annis ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Response Dynamics ◽  
Shock Response ◽  
Age Dependent

scholarly journals Microfluidics: Stochastic and Age‐Dependent Proteostasis Decline Underlies Heterogeneity in Heat‐Shock Response Dynamics (Small 30/2021)

Small ◽  
2021 ◽  
Vol 17 (30) ◽  
pp. 2170157
Author(s):  
Nadia Vertti‐Quintero ◽  
Simon Berger ◽  
Xavier Casadevall i Solvas ◽  
Cyril Statzer ◽  
Jillian Annis ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Response Dynamics ◽  
Shock Response ◽  
Age Dependent

scholarly journals Diversification of the Caenorhabditis heat shock response by Helitron transposable elements

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jacob M Garrigues ◽  
Brian V Tsu ◽  
Matthew D Daugherty ◽  
Amy E Pasquinelli
Keyword(s):  
Heat Shock ◽  
Rna Polymerase Ii ◽  
Heat Shock Response ◽  
Heat Shock Factor 1 ◽  
Cellular Protection ◽  
C Elegans ◽  
Expression Of Genes ◽  
Shock Response ◽  
Caenorhabditis Species ◽  
Species Specific

Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans. Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans. Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR.

scholarly journals Caenorhabditis elegans AF4/FMR2 family homolog affl-2 is required for heat shock induced gene expression

2019 ◽  
Author(s):  
Sophie J. Walton ◽  
Han Wang ◽  
Porfirio Quintero-Cadena ◽  
Alex Bateman ◽  
Paul W. Sternberg
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Genetic Locus ◽  
Transcriptional Response ◽  
Egg Laying ◽  
Transcriptional Elongation ◽  
C Elegans ◽  
Shock Response

AbstractTo mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat shock induced gene expression in C. elegans, we identified a new allele of hsf-1 that alters its DNA-binding domain, and three additional alleles of sup-45, a previously uncharacterized genetic locus. We identified sup-45 as one of the two hitherto unknown C. elegans orthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamed sup-45 as affl-2 (AF4/FMR2-Like). affl-2 mutants are egg-laying defective and dumpy, but worms lacking its sole paralog (affl-1) appear wild-type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response. affl-2 and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests that affl-2 may function downstream or parallel of hsf-1. Our characterization of affl-2 provides insights into the complex processes of transcriptional elongation and regulating heat shock induced gene expression to protect against heat stress.

scholarly journals Mathematical Modeling of the Eukaryotic Heat-Shock Response: Dynamics of the hsp70 Promoter

2005 ◽  
Vol 88 (3) ◽  
pp. 1646-1658 ◽  
Author(s):  
Theodore R. Rieger ◽  
Richard I. Morimoto ◽  
Vassily Hatzimanikatis
Keyword(s):  
Mathematical Modeling ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Response Dynamics ◽  
Hsp70 Promoter ◽  
Shock Response

scholarly journals Role of vapBC toxin–antitoxin loci in the thermal stress response of Sulfolobus solfataricus

2009 ◽  
Vol 37 (1) ◽  
pp. 123-126 ◽  
Author(s):  
Charlotte R. Cooper ◽  
Amanda J. Daugherty ◽  
Sabrina Tachdjian ◽  
Paul H. Blum ◽  
Robert M. Kelly
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Sulfolobus Solfataricus ◽  
Temperature Shift ◽  
Transcriptional Analysis ◽  
Response Dynamics ◽  
Shock Response ◽  
Impact On Survival

TA (toxin–antitoxin) loci are ubiquitous in prokaryotic micro-organisms, including archaea, yet their physiological function is largely unknown. For example, preliminary reports have suggested that TA loci are microbial stress-response elements, although it was recently shown that knocking out all known chromosomally located TA loci in Escherichia coli did not have an impact on survival under certain types of stress. The hyperthermophilic crenarchaeon Sulfolobus solfataricus encodes at least 26 vapBC (where vap is virulence-associated protein) family TA loci in its genome. VapCs are PIN (PilT N-terminus) domain proteins with putative ribonuclease activity, while VapBs are proteolytically labile proteins, which purportedly function to silence VapCs when associated as a cognate pair. Global transcriptional analysis of S. solfataricus heat-shock-response dynamics (temperature shift from 80 to 90°C) revealed that several vapBC genes were triggered by the thermal shift, suggesting a role in heat-shock-response. Indeed, knocking out a specific vapBC locus in S. solfataricus substantially changed the transcriptome and, in one case, rendered the crenarchaeon heat-shock-labile. These findings indicate that more work needs to be done to determine the role of VapBCs in S. solfataricus and other thermophilic archaea, especially with respect to post-transcriptional regulation.

scholarly journals Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response

2016 ◽  
Vol 114 (2) ◽  
pp. E152-E160 ◽  
Author(s):  
Matthias C. Truttmann ◽  
Xu Zheng ◽  
Leo Hanke ◽  
Jadyn R. Damon ◽  
Monique Grootveld ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Heat Shock ◽  
Protein Aggregation ◽  
Heat Shock Response ◽  
Protein Translation ◽  
Cellular Protein ◽  
Interacting Protein ◽  
Endogenous Protein ◽  
Shock Response ◽  
Influenza Virus Replication

Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes—huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively—in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality. Overexpression of Ssa2, a cytosolic heat shock protein (Hsp)70, was sufficient to partially rescue growth. In human cell lines, overexpression of active HYPE similarly induced protein aggregation and the HSF1-dependent heat shock response. Excessive AMPylation also abolished HSP70-dependent influenza virus replication. Our findings suggest a mode of Hsp70 inactivation by AMPylation and point toward a role for protein AMPylation in the regulation of cellular protein homeostasis beyond the endoplasmic reticulum.

Sign in / Sign up

Export Citation Format

Share Document