scholarly journals The coupling of translational control and stress responses

2020 ◽  
Vol 168 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Ryan Houston ◽  
Shiori Sekine ◽  
Yusuke Sekine
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Translational Control ◽  
Messenger Rna ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Translation Rate ◽  
Nucleolar Stress ◽  
Multistep Process ◽  
Aminoacyl Transfer

Abstract The translation of messenger RNA (mRNA) into protein is a multistep process by which genetic information transcribed into an mRNA is decoded to produce a specific polypeptide chain of amino acids. Ribosomes play a central role in translation by coordinately working with various translation regulatory factors and aminoacyl-transfer RNAs. Various stresses attenuate the ribosomal synthesis in the nucleolus as well as the translation rate in the cytosol. To efficiently reallocate cellular energy and resources, mammalian cells are endowed with mechanisms that directly link the suppression of translation-related processes to the activation of stress adaptation programmes. This review focuses on the integrated stress response (ISR) and the nucleolar stress response (NSR) both of which are activated by various stressors and selectively upregulate stress-responsive transcription factors. Emerging findings have delineated the detailed molecular mechanisms of the ISR and NSR and expanded their physiological and pathological significances.

scholarly journals Conserved Roles of C. elegans and Human MANFs in Sulfatide Binding and Cytoprotection

2018 ◽  
Author(s):  
Meirong Bai ◽  
Roman Vozdek ◽  
Aleš Hnízda ◽  
Chenxiao Jiang ◽  
Bingying Wang ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Dopamine Neurons ◽  
Lipid Mediator ◽  
Outer Cell ◽  
Dependent Manner ◽  
C Elegans ◽  
Er Stress Response

AbstractMesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protect dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF’s cytoprotection.

scholarly journals Multilevel regulation of endoplasmic reticulum stress responses in plants: where old roads and new paths meet

2019 ◽  
Vol 71 (5) ◽  
pp. 1659-1667 ◽  
Author(s):  
Taiaba Afrin ◽  
Danish Diwan ◽  
Katrina Sahawneh ◽  
Karolina Pajerowska-Mukhtar
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Stress Responses ◽  
Translational Control ◽  
Protein Quality ◽  
Unfolded Protein ◽  
Transcriptional Gene Regulation ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract The sessile lifestyle of plants requires them to cope with a multitude of stresses in situ. In response to diverse environmental and intracellular cues, plant cells respond by massive reprogramming of transcription and translation of stress response regulators, many of which rely on endoplasmic reticulum (ER) processing. This increased protein synthesis could exceed the capacity of precise protein quality control, leading to the accumulation of unfolded and/or misfolded proteins that triggers the unfolded protein response (UPR). Such cellular stress responses are multilayered and executed in different cellular compartments. Here, we will discuss the three main branches of UPR signaling in diverse eukaryotic systems, and describe various levels of ER stress response regulation that encompass transcriptional gene regulation by master transcription factors, post-transcriptional activities including cytoplasmic splicing, translational control, and multiple post-translational events such as peptide modifications and cleavage. In addition, we will discuss the roles of plant ER stress sensors in abiotic and biotic stress responses and speculate on the future prospects of engineering these signaling events for heightened stress tolerance.

scholarly journals A Systematic View Exploring the Role of Chloroplasts in Plant Abiotic Stress Responses

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yo-Han Yoo ◽  
Woo-Jong Hong ◽  
Ki-Hong Jung
Keyword(s):  
Abiotic Stress ◽  
High Temperature ◽  
Stress Response ◽  
Temperature Stress ◽  
Stress Responses ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Close Association ◽  
High Temperature Stress ◽  
Growth And Yield

Chloroplasts are intracellular semiautonomous organelles central to photosynthesis and are essential for plant growth and yield. The significance of the function of chloroplast-related genes in response to climate change has not been well studied in crops. In the present study, the initial focus was on genes that were predicted to be located in the chloroplast genome in rice, a model crop plant, with genes either preferentially expressed in the leaf or ubiquitously expressed in all organs. The characteristics were analyzed by Gene Ontology (GO) enrichment and MapMan functional classification tools. It was then identified that 110 GO terms (45 for leaf expression and 65 for ubiquitous expression) and 1,695 genes mapped to MapMan overviews were strongly associated with chloroplasts. In particular, the MapMan cellular response overview revealed a close association between heat stress response and chloroplast-related genes in rice. Moreover, features of these genes in response to abiotic stress were analyzed using a large-scale publicly available transcript dataset. Consequently, the expression of 215 genes was found to be upregulated in response to high temperature stress. Conversely, genes that responded to other stresses were extremely limited. In other words, chloroplast-related genes were found to affect abiotic stress response mainly through high temperature response, with little effect on response to drought and salinity stress. These results suggest that genes involved in diurnal rhythm in the leaves participate in the reaction to recognize temperature changes in the environment. Furthermore, the predicted protein–protein interaction network analysis associated with high temperature stress is expected to provide a very important basis for the study of molecular mechanisms by which chloroplasts will respond to future climate changes.

scholarly journals The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

2020 ◽  
Author(s):  
Sarel J. Urso ◽  
Marcella Comly ◽  
John A. Hanover ◽  
Todd Lamitina
Keyword(s):  
Stress Response ◽  
Cell Volume ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cell Physiology ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Intracellular Proteins ◽  
Molecular Functions ◽  
Glcnac Transferase

AbstractThe conserved O-GlcNAc transferase OGT O-GlcNAcylates serine and threonine residues of intracellular proteins to regulate their function. OGT is required for viability in mammalian cells, but its specific roles in cellular physiology are poorly understood. Here we describe a conserved requirement for OGT in an essential aspect of cell physiology: the hypertonic stress response. Through a forward genetic screen in Caenorhabditis elegans, we discovered OGT is acutely required for osmoprotective protein expression and adaptation to hypertonic stress. Gene expression analysis shows that ogt-1 functions through a post-transcriptional mechanism. Human OGT partially rescues the C. elegans phenotypes, suggesting that the osmoregulatory functions of OGT are ancient. Intriguingly, mutations that ablate O-GlcNAcylation activity in either human or C. elegans OGT rescue the hypertonic stress response phenotype. Our findings are among the first to demonstrate a specific physiological role for OGT at the organismal level and demonstrate that OGT engages in important molecular functions outside of its well described roles in post-translational O-GlcNAcylation of intracellular proteins.Author SummaryThe ability to sense and adapt to changes in the environment is an essential feature of cellular life. Changes in environmental salt and water concentrations can rapidly cause cell volume swelling or shrinkage and, if left unchecked, will lead to cell and organismal death. All organisms have developed similar physiological strategies for maintaining cell volume. However, the molecular mechanisms that control these physiological outputs are not well understood in animals. Using unbiased genetic screening in C. elegans, we discovered that a highly conserved enzyme called O-GlcNAc transferase (OGT) is essential for regulating physiological responses to increased environmental solute levels. A human form of OGT can functionally substitute for worm OGT, showing that this role is conserved across evolution. Surprisingly, the only known enzymatic activity of OGT was not required for this role, suggesting this enzyme has important undescribed molecular functions. Our studies reveal a new animal-specific role for OGT in the response to osmotic stress and show that C. elegans is an important model for defining the conserved molecular mechanisms that respond to alterations in cell volume.

scholarly journals Signaling Overlap between the Golgi Stress Response and Cysteine Metabolism in Huntington’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1468
Author(s):  
Bindu D. Paul
Keyword(s):  
Stress Response ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Corpus Striatum ◽  
Cellular Processes ◽  
Er Stress Response ◽  
Cysteine Metabolism ◽  
The Brain

Huntington’s disease (HD) is caused by expansion of polyglutamine repeats in the protein huntingtin, which affects the corpus striatum of the brain. The polyglutamine repeats in mutant huntingtin cause its aggregation and elicit toxicity by affecting several cellular processes, which include dysregulated organellar stress responses. The Golgi apparatus not only plays key roles in the transport, processing, and targeting of proteins, but also functions as a sensor of stress, signaling through the Golgi stress response. Unlike the endoplasmic reticulum (ER) stress response, the Golgi stress response is relatively unexplored. This review focuses on the molecular mechanisms underlying the Golgi stress response and its intersection with cysteine metabolism in HD.

scholarly journals Cellular responses to reactive oxygen species can be predicted on multiple biological scales from molecular mechanisms

2017 ◽  
Author(s):  
Laurence Yang ◽  
Nathan Mih ◽  
Amitesh Anand ◽  
Joon Ho Park ◽  
Justin Tan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stress Response ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Multi Scale ◽  
Genome Wide ◽  
Universal Common Ancestor ◽  
A Genome

SummaryCatalysis using iron-sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can completely inhibit cell growth when unmanaged and thus elicits an essential stress response that is universal and fundamental in biology. We develop a computable multi-scale description of the ROS stress response in Escherichia coli. We show that this quantitative framework allows for the understanding and prediction of ROS stress responses at three levels: 1) pathways: amino acid auxotrophies, 2) networks: the systemic response to ROS stress, and 3) genetic basis: adaptation to ROS stress during laboratory evolution. These results show that we can now develop fundamental and quantitative genotype-phenotype relationships for stress responses on a genome-wide basis.

scholarly journals A conserved role of CBP/p300 in mitochondrial stress response and longevity

2020 ◽  
Author(s):  
Terytty Yang Li ◽  
Maroun Bou Sleiman ◽  
Hao Li ◽  
Arwen W. Gao ◽  
Adrienne Mottis ◽  
...  
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Amyloid Β ◽  
Human Populations ◽  
Histone Demethylases ◽  
Mitochondrial Stress ◽  
Unfolded Protein ◽  
Evolutionarily Conserved ◽  
Protein Response

Abstract Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how different layers of UPRmt regulators are orchestrated to transcriptionally activate the stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator for UPRmt activation, as well as for mitochondrial stress-induced immune response, reduction of amyloid-β aggregation and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.

scholarly journals Cellular responses to reactive oxygen species are predicted from molecular mechanisms

2019 ◽  
Vol 116 (28) ◽  
pp. 14368-14373 ◽  
Author(s):  
Laurence Yang ◽  
Nathan Mih ◽  
Amitesh Anand ◽  
Joon Ho Park ◽  
Justin Tan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stress Response ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
A Genome

Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a computable multiscale description of the ROS stress response inEscherichia coli, called OxidizeME. We use OxidizeME to explain four key responses to oxidative stress: 1) ROS-induced auxotrophy for branched-chain, aromatic, and sulfurous amino acids; 2) nutrient-dependent sensitivity of growth rate to ROS; 3) ROS-specific differential gene expression separate from global growth-associated differential expression; and 4) coordinated expression of iron–sulfur cluster (ISC) and sulfur assimilation (SUF) systems for iron–sulfur cluster biosynthesis. These results show that we can now develop fundamental and quantitative genotype–phenotype relationships for stress responses on a genome-wide basis.

scholarly journals A Deregulated Stress Response Underlies Distinct INF2-Associated Disease Profiles

2020 ◽  
Vol 31 (6) ◽  
pp. 1296-1313 ◽  
Author(s):  
Samet Bayraktar ◽  
Julian Nehrig ◽  
Ekaterina Menis ◽  
Kevser Karli ◽  
Annette Janning ◽  
...  
Keyword(s):  
Stress Response ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Calcium Influx ◽  
Medical Diagnostics ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Monogenic Diseases ◽  
Tooth Disease

BackgroundMonogenic diseases provide favorable opportunities to elucidate the molecular mechanisms of disease progression and improve medical diagnostics. However, the complex interplay between genetic and environmental factors in disease etiologies makes it difficult to discern the mechanistic links between different alleles of a single locus and their associated pathophysiologies. Inverted formin 2 (INF2), an actin regulator, mediates a stress response—calcium mediated actin reset, or CaAR—that reorganizes the actin cytoskeleton of mammalian cells in response to calcium influx. It has been linked to the podocytic kidney disease focal segemental glomerulosclerosis (FSGS), as well as to cases of the neurologic disorder Charcot–Marie–Tooth disease that are accompanied by nephropathy, mostly FSGS.MethodsWe used a combination of quantitative live cell imaging and validation in primary patient cells and Drosophila nephrocytes to systematically characterize a large panel of >50 autosomal dominant INF2 mutants that have been reported to cause either FSGS alone or with Charcot–Marie–Tooth disease.ResultsWe found that INF2 mutations lead to deregulated activation of formin and a constitutive stress response in cultured cells, primary patient cells, and Drosophila nephrocytes. We were able to clearly distinguish between INF2 mutations that were linked exclusively to FSGS from those that caused a combination of FSGS and Charcot–Marie–Tooth disease. Furthermore, we were able to identify distinct subsets of INF2 variants that exhibit varying degrees of activation.ConclusionsOur results suggest that CaAR can be used as a sensitive assay for INF2 function and for robust evaluation of diseased-linked variants of formin. More broadly, these findings indicate that cellular profiling of disease-associated mutations has potential to contribute substantially to sequence-based phenotype predictions.

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