Special Issue "Cellular Stress Response in Health and Disease"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 October 2018)

Special Issue Editor

Guest Editor
Dr. Alessandra Stacchiotti

Division of Human Anatomy, Department Clinical and Experimental Sciences, Brescia University, Italy
Website | E-Mail
Interests: ER stress; aging; obesity; mitochondria damage; microscopy

Special Issue Information

Dear Colleagues,

Stress is implied in cellular life, and according to the “hormesis principle”, a mild cellular stress is sometimes useful to best react against a more severe insult. Historically, we owe the seminal discovery of the “heat stress response” to the Italian scientist Ferruccio Ritossa in the 1960s, which demonstrated an intense transcriptional activity in chromosomal puffs in heated Drosophila salivary glands. Afterwards, heat shock proteins (HSPs) have been characterized not only in hyperthermia but also in the response to environmental, metabolic, or toxic inputs. In aging, a stressful reaction occurs because stress proteins are reduced. However, HSPs are not only inside cells but also in the extracellular environment in cancer, inflammation, and intercellular communication through exosomes. Besides classical HSPs, when homeostasis is disrupted, abnormal endoplasmic reticulum (ER) and mitochondrial stress triggers the unfolded protein response (UPR). This mechanism is dramatically involved in the pathogenesis of cancer, neurodegenerative diseases like Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis, in retinal damage, and in cardiovascular and metabolic morbidities. So, strategies aimed at modulating ER stress or mitochondrial response are crucial. This Special Issue offers an Open Access forum that aims to bring together a collection of original research and review articles addressing the expanding field of cellular stress response and modulation. We hope to provide a stimulating resource for the fascinating subject of cell stress research. Suggested potential topics may be: hormesis; ER stress and mitochondrial stress in diseases; the role of HSPs in exercise and in longevity; molecular chaperones as therapeutic targets; exosomes and HSPs; and new models to study stress response

Dr. Alessandra Stacchiotti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • heat shock proteins
  • mitochondria-associated membranes
  • neurodegenerative disorders
  • ER stress response and UPR
  • metabolic disorders

Published Papers (6 papers)

View options order results:
result details:
Displaying articles 1-6
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Proteomic Signatures of Clostridium difficile Stressed with Metronidazole, Vancomycin, or Fidaxomicin
Cells 2018, 7(11), 213; https://doi.org/10.3390/cells7110213
Received: 24 October 2018 / Revised: 12 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
PDF Full-text (1983 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The anaerobic pathogen Clostridium difficile is of growing significance for the health care system due to its increasing incidence and mortality. As C. difficile infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of
[...] Read more.
The anaerobic pathogen Clostridium difficile is of growing significance for the health care system due to its increasing incidence and mortality. As C. difficile infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of C. difficile 630∆erm to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of C. difficile allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Graphical abstract

Open AccessArticle Insertion Defects of Mitochondrially Encoded Proteins Burden the Mitochondrial Quality Control System
Cells 2018, 7(10), 172; https://doi.org/10.3390/cells7100172
Received: 14 September 2018 / Revised: 7 October 2018 / Accepted: 16 October 2018 / Published: 17 October 2018
PDF Full-text (2200 KB) | HTML Full-text | XML Full-text
Abstract
The mitochondrial proteome contains proteins from two different genetic systems. Proteins are either synthesized in the cytosol and imported into the different compartments of the organelle or directly produced in the mitochondrial matrix. To ensure proteostasis, proteins are monitored by the mitochondrial quality
[...] Read more.
The mitochondrial proteome contains proteins from two different genetic systems. Proteins are either synthesized in the cytosol and imported into the different compartments of the organelle or directly produced in the mitochondrial matrix. To ensure proteostasis, proteins are monitored by the mitochondrial quality control system, which will degrade non-native polypeptides. Defective mitochondrial membrane proteins are degraded by membrane-bound AAA-proteases. These proteases are regulated by factors promoting protein turnover or preventing their degradation. Here we determined genetic interactions between the mitoribosome receptors Mrx15 and Mba1 with the quality control system. We show that simultaneous absence of Mrx15 and the regulators of the i-AAA protease Mgr1 and Mgr3 provokes respiratory deficiency. Surprisingly, mutants lacking Mrx15 were more tolerant against proteotoxic stress. Furthermore, yeast cells became hypersensitive against proteotoxic stress upon deletion of MBA1. Contrary to Mrx15, Mba1 cooperates with the regulators of the m-AAA and i-AAA proteases. Taken together, these results suggest that membrane protein insertion and mitochondrial AAA-proteases are functionally coupled, possibly reflecting an early quality control step during mitochondrial protein synthesis. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Graphical abstract

Open AccessArticle Interplay between Endoplasmic Reticular Stress and Survivin in Colonic Epithelial Cells
Cells 2018, 7(10), 171; https://doi.org/10.3390/cells7100171
Received: 24 August 2018 / Revised: 9 October 2018 / Accepted: 11 October 2018 / Published: 15 October 2018
PDF Full-text (3928 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a
[...] Read more.
Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a mechanism adopted by cancer cells with the help of the inhibitor of an apoptosis (IAP) class of proteins such as Survivin to evade cell death and gain a proliferative advantage. In this study, we aimed to reveal the interrelation between ERS and Survivin. We initially verified the expression of Survivin in Winnie (a mouse model of chronic ERS) colon tissues by using immunohistochemistry (IHC) and immunofluorescence (IF) in comparison with wild type Blk6 mice. Additionally, we isolated the goblet cells and determined the expression of Survivin by IF and protein validation. Tunicamycin was utilized at a concentration of 10 µg/mL to induce ERS in the LS174T cell line and the gene expression of the ERS markers was measured. This was followed by determination of inflammatory cytokines. Inhibition of ERS was carried out by 4Phenyl Butyric acid (4PBA) at a concentration of 10 mM to assess whether there was a reciprocation effect. The downstream cell death assays including caspase 3/7, Annexin V, and poly(ADP-ribose) polymerase (PARP) cleavage were evaluated in the presence of ERS and absence of ERS, which was followed by a proliferative assay (EdU click) with and without ERS. Correspondingly, we inhibited Survivin by YM155 at a concentration of 100 nM and observed the succeeding ERS markers and inflammatory markers. We also verified the caspase 3/7 assay. Our results demonstrate that ERS inhibition not only significantly reduced the UPR genes (Grp78, ATF6, PERK and XBP1) along with Survivin but also downregulated the inflammatory markers such as IL8, IL4, and IL6, which suggests a positive correlation between ERS and the inhibition of apoptosis. Furthermore, we provided evidence that ERS inhibition promoted apoptosis in LS174T cells and shortened the proliferation rate. Moreover, Survivin inhibition by YM155 led to a comparable effect as that of ERS inhibition, which includes attenuation of ERS genes and inflammatory markers as well as the promotion of programmed cell death via the caspase 3/7 pathway. Together, our results propose the interrelation between ERS and inhibition of apoptosis assigning a molecular and therapeutic target for cancer treatment. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Graphical abstract

Review

Jump to: Research

Open AccessReview Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells
Received: 12 May 2018 / Revised: 20 June 2018 / Accepted: 25 June 2018 / Published: 29 June 2018
Cited by 1 | PDF Full-text (1793 KB) | HTML Full-text | XML Full-text
Abstract
Innate and adaptive immune cells from myeloid and lymphoid lineages resolve host infection or cell stress by mounting an appropriate and durable immune response. Upon sensing of cellular insults, immune cells become activated and undergo rapid and efficient functional changes to unleash biosynthesis
[...] Read more.
Innate and adaptive immune cells from myeloid and lymphoid lineages resolve host infection or cell stress by mounting an appropriate and durable immune response. Upon sensing of cellular insults, immune cells become activated and undergo rapid and efficient functional changes to unleash biosynthesis of macromolecules, proliferation, survival, and trafficking; unprecedented events among other mammalian cells within the host. These changes must become operational within restricted timing to rapidly control the insult and to avoid tissue damage and pathogen spread. Such changes occur at high energy cost. Recent advances have established that plasticity of immune functions occurs in distinct metabolic stress features. Evidence has accumulated to indicate that specific metabolic signatures dictate appropriate immune functions in both innate and adaptive immunity. Importantly, recent studies have shed light on whether successfully manipulating particular metabolic targets is sufficient to modulate immune function and polarization, thereby offering strong therapeutic potential for various common immune-mediated diseases, including inflammation and autoimmune-associated diseases and cancer. In this review, we detail how cellular metabolism controls immune function and phenotype within T cells and macrophages particularly, and the distinct molecular metabolic programming and targets instrumental to engage this regulation. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Figure 1

Open AccessReview Endoplasmic Reticulum Stress in Metabolic Disorders
Received: 14 May 2018 / Revised: 12 June 2018 / Accepted: 14 June 2018 / Published: 19 June 2018
Cited by 5 | PDF Full-text (1252 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these diseases has
[...] Read more.
Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these diseases has different physiological and clinical symptoms, they appear to share certain pathological traits such as intracellular stress and inflammation induced by metabolic disturbance stemmed from over nutrition frequently aggravated by a modern, sedentary life style. These modern ways of living inundate cells and organs with saturating levels of sugar and fat, leading to glycotoxicity and lipotoxicity that induce intracellular stress signaling ranging from oxidative to ER stress response to cope with the metabolic insults (Mukherjee, et al., 2015). In this review, we discuss the roles played by cellular stress and its responses in shaping metabolic disorders. We have summarized here current mechanistic insights explaining the pathogenesis of these disorders. These are followed by a discussion of the latest therapies targeting the stress response pathways. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Figure 1

Open AccessFeature PaperReview Unfolding the Endoplasmic Reticulum of a Social Amoeba: Dictyostelium discoideum as a New Model for the Study of Endoplasmic Reticulum Stress
Received: 26 April 2018 / Revised: 28 May 2018 / Accepted: 5 June 2018 / Published: 10 June 2018
Cited by 1 | PDF Full-text (2567 KB) | HTML Full-text | XML Full-text
Abstract
The endoplasmic reticulum (ER) is a membranous network with an intricate dynamic architecture necessary for various essential cellular processes. Nearly one third of the proteins trafficking through the secretory pathway are folded and matured in the ER. Additionally, it acts as calcium storage,
[...] Read more.
The endoplasmic reticulum (ER) is a membranous network with an intricate dynamic architecture necessary for various essential cellular processes. Nearly one third of the proteins trafficking through the secretory pathway are folded and matured in the ER. Additionally, it acts as calcium storage, and it is a main source for lipid biosynthesis. The ER is highly connected with other organelles through regions of membrane apposition that allow organelle remodeling, as well as lipid and calcium traffic. Cells are under constant changes due to metabolic requirements and environmental conditions that challenge the ER network’s maintenance. The unfolded protein response (UPR) is a signaling pathway that restores homeostasis of this intracellular compartment upon ER stress conditions by reducing the load of proteins, and by increasing the processes of protein folding and degradation. Significant progress on the study of the mechanisms that restore ER homeostasis was achieved using model organisms such as yeast, Arabidopsis, and mammalian cells. In this review, we address the current knowledge on ER architecture and ER stress response in Dictyostelium discoideum. This social amoeba alternates between unicellular and multicellular phases and is recognized as a valuable biomedical model organism and an alternative to yeast, particularly for the presence of traits conserved in animal cells that were lost in fungi. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
Figures

Figure 1

Back to Top