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Frontiers in Immunology 2023Eukaryotic cells are stimulated by external pressure such as that derived from heat shock, oxidative stress, nutrient deficiencies, or infections, which induce the... (Review)
Review
Eukaryotic cells are stimulated by external pressure such as that derived from heat shock, oxidative stress, nutrient deficiencies, or infections, which induce the formation of stress granules (SGs) that facilitates cellular adaptation to environmental pressures. As aggregated products of the translation initiation complex in the cytoplasm, SGs play important roles in cell gene expression and homeostasis. Infection induces SGs formation. Specifically, a pathogen that invades a host cell leverages the host cell translation machinery to complete the pathogen life cycle. In response, the host cell suspends translation, which leads to SGs formation, to resist pathogen invasion. This article reviews the production and function of SGs, the interaction between SGs and pathogens, and the relationship between SGs and pathogen-induced innate immunity to provide directions for further research into anti-infection and anti-inflammatory disease strategies.
Topics: Cytoplasmic Granules; Stress Granules; Cytoplasm; Oxidative Stress; Heat-Shock Response
PubMed: 37205103
DOI: 10.3389/fimmu.2023.1145346 -
Chemical Research in Toxicology Oct 2020Vitamin C (ascorbic acid) is a water-soluble antioxidant and a cofactor for a large number of enzymes. It is present in all tissues and especially abundant in corneal... (Review)
Review
Vitamin C (ascorbic acid) is a water-soluble antioxidant and a cofactor for a large number of enzymes. It is present in all tissues and especially abundant in corneal epithelium, stem cells, and neurons. Although similar to thiols in its ability to react with many reactive oxygen species (ROS), ascorbate is much better (>100× faster) than glutathione at scavenging of primary ROS (superoxide radical and singlet oxygen). Ascorbate appears to be especially important for elimination of O in the nucleus which contains little or no SOD activity. Cofactor functions of ascorbate involve the maintenance of activity of Fe(II)/2-oxoglutarate-dependent dioxygenases via reduction of Fe(III). The most prominent activity of ascorbate-dependent dioxygenases in the cytoplasm is hydroxylation of prolines in proteins involved in the formation of extracellular matrix and regulation of metabolism and hypoxia responses. In the nucleus, ascorbate is important for oxidative demethylation of 5-methylcytosine in DNA (by TET proteins) and removal of methyl groups from histone lysines (by JmjC demethylases). Differentiation and other cellular reprograming processes involving DNA demethylation are especially sensitive to ascorbate insufficiency. High doses of vitamin C alone or in combinations with drugs produced cancer-suppressive effects which involved redox, immune, and epigenetic mechanisms. Solutions to vitamin C deficiency in cultured cells are discussed to improve the physiological relevance of models. An abundance of vitamin C in rodents limits their ability to fully recapitulate human sensitivity to adverse health effects of malnutrition and xenobiotics, including neurotoxicity, lung injury, and intergenerational and other epigenetic effects.
Topics: Animals; Ascorbic Acid; Cell Nucleus; Cytoplasm; DNA; Humans
PubMed: 33001635
DOI: 10.1021/acs.chemrestox.0c00348 -
Traffic (Copenhagen, Denmark) Feb 2014Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Because of its critical function in many cellular processes,... (Review)
Review
Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Because of its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, whereas viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. As viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. This review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens.
Topics: Active Transport, Cell Nucleus; Animals; Cell Nucleus; Cytoplasm; Humans; RNA Transport; Viruses
PubMed: 24289861
DOI: 10.1111/tra.12137 -
Cell May 2016Over a century ago, colloidal phase separation of matter into non-membranous bodies was recognized as a fundamental organizing principal of cell "protoplasm." Recent... (Review)
Review
Over a century ago, colloidal phase separation of matter into non-membranous bodies was recognized as a fundamental organizing principal of cell "protoplasm." Recent insights into the molecular properties of such phase-separated bodies present challenges to our understanding of cellular protein interaction networks, as well as opportunities for interpreting and understanding of native and pathological genetic and molecular interactions. Here, we briefly review examples of and discuss physical principles of phase-separated cellular bodies and then reflect on how knowledge of these principles may direct future research on their functions.
Topics: Animals; Colloids; Cytoplasm; Dequalinium; Humans; Organelles; Protein Interaction Mapping; Proteins
PubMed: 27203111
DOI: 10.1016/j.cell.2016.05.026 -
Methods in Molecular Biology (Clifton,... 2012Astrocytes participate in all essential CNS functions, including blood flow regulation, energy metabolism, ion and water homeostasis, immune defence, neurotransmission,... (Review)
Review
Astrocytes participate in all essential CNS functions, including blood flow regulation, energy metabolism, ion and water homeostasis, immune defence, neurotransmission, and adult neurogenesis. It is thus not surprising that astrocytic morphology and function differ between regions, and that different subclasses of astrocytes exist within the same brain region. Recent lines of work also show that the complexity of protoplasmic astrocytes increases during evolution. Human astrocytes are structurally more complex, larger, and propagate calcium signals significantly faster than rodent astrocytes. In this chapter, we review the diversity of astrocytic form and function, while considering the markedly expanded roles of astrocytes with phylogenetic evolution. We also define major challenges for the future, which include determining how astrocytic functions are locally specified, defining the molecular controls upon astrocytic fate and physiology and establishing how evolutionary changes in astrocytes contribute to higher cognitive functions.
Topics: Animals; Astrocytes; Biological Evolution; Calcium; Cognition; Cytoplasm; Glutamate Plasma Membrane Transport Proteins; Glutamic Acid; Humans; Receptors, Neurotransmitter; Species Specificity
PubMed: 22144298
DOI: 10.1007/978-1-61779-452-0_3 -
The EMBO Journal Jun 2018Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they... (Review)
Review
Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change. Cellular stresses such as starvation and invasion are internal insults that evoke changes in droplet metabolism and dynamics. This review will first outline lipid droplet assembly and then discuss how droplets respond to stress and in particular nutrient starvation. Finally, the role of droplets in viral and microbial invasion will be presented, where an unresolved issue is whether changes in droplet abundance promote the invader, defend the host, to try to do both. The challenges of stress and infection are often accompanied by changes in physical contacts between droplets and other organelles. How these changes may result in improving cellular physiology, an ongoing focus in the field, is discussed.
Topics: Animals; Bacterial Infections; Cytoplasm; Humans; Lipid Droplets; Stress, Physiological; Virus Diseases
PubMed: 29789390
DOI: 10.15252/embj.201898947 -
Nature Reviews. Molecular Cell Biology Mar 2021Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of... (Review)
Review
Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties and regulation arise from molecular constituents. Recent years have brought a focus on understanding condensate functions. Studies have revealed functions that span different length scales: from molecular (modulating the rates of chemical reactions) to mesoscale (organizing large structures within cells) to cellular (facilitating localization of cellular materials and homeostatic responses). In this Roadmap, we discuss representative examples of biochemical and cellular functions of biomolecular condensates from the recent literature and organize these functions into a series of non-exclusive classes across the different length scales. We conclude with a discussion of areas of current interest and challenges in the field, and thoughts about how progress may be made to further our understanding of the widespread roles of condensates in cell biology.
Topics: Animals; Biochemical Phenomena; Cell Physiological Phenomena; Cytoplasm; Eukaryotic Cells; Humans; Macromolecular Substances; Multiprotein Complexes; Organelles; Protein Aggregates
PubMed: 33169001
DOI: 10.1038/s41580-020-00303-z -
Cancer Biology & Therapy Jan 2011Autophagy is a self-catabolic process that maintains intracellular homeostasis and prolongs cell survival under stress via lysosomal degradation of cytoplasmic... (Review)
Review
Autophagy is a self-catabolic process that maintains intracellular homeostasis and prolongs cell survival under stress via lysosomal degradation of cytoplasmic constituents and recycling of amino acids and energy. Autophagy is intricately involved in many aspects of human health and disease, including cancer. Autophagy is a double-edged sword in tumorigenesis, acting both as a tumor suppressor and a protector of cancer cell survival, and elucidation of its exact role at different stages of cancer progression and in treatment responsiveness is a complex and challenging task. Better understanding of autophagy regulation and its impact on treatment outcome will potentially allow us to identify novel therapeutic targets in cancer. In this review, we summarize current knowledge on the regulation and dual function of autophagy in tumorigenesis, as well as ongoing efforts in modulating autophagy for cancer treatment and prevention. This is a very exciting and highly promising area of cancer research, as pharmacologic modulation of autophagy appears to augment the efficacy of currently available anticancer regimens and opens the way to the development of new combinatorial therapeutic strategies that will hopefully contribute to cancer eradication.
Topics: Autophagy; Cell Survival; Clinical Trials as Topic; Cytoplasm; Genes, Tumor Suppressor; Humans; Neoplasms
PubMed: 21228626
DOI: 10.4161/cbt.11.2.14622 -
Cell Communication and Signaling : CCS Nov 2018Tunnelling nanotubes (TNTs), also known as membrane nanochannels, are actin-based structures that facilitate cytoplasmic connections for rapid intercellular transfer of... (Review)
Review
Tunnelling nanotubes (TNTs), also known as membrane nanochannels, are actin-based structures that facilitate cytoplasmic connections for rapid intercellular transfer of signals, organelles and membrane components. These dynamic TNTs can form de novo in animal cells and establish complex intercellular networks between distant cells up to 150 μm apart. Within the last decade, TNTs have been discovered in different cell types including tumor cells, macrophages, monocytes, endothelial cells and T cells. It has also been further elucidated that these nanotubes play a vital role in diseased conditions such as cancer, where TNT formation occurs at a higher pace and is used for rapid intercellular modulation of chemo-resistance. Viruses such as HIV, HSV and prions also hijack the existing TNT connections between host cells for rapid transmission and evasion of the host immune responses. The following review aims to describe the heterogeneity of TNTs, their role in different tissues and disease conditions in order to enhance our understanding on how these nanotubes can be used as a target for therapies.
Topics: Animals; Biological Transport; Cell Communication; Cytoplasm; Disease; Endothelial Cells; Humans; Neoplasms
PubMed: 30409198
DOI: 10.1186/s12964-018-0281-7 -
Current Opinion in Cell Biology Aug 2009The endoplasmic reticulum (ER) is a single continuous membrane-enclosed organelle made up of functionally and structurally distinct domains. The ER domains include the... (Review)
Review
The endoplasmic reticulum (ER) is a single continuous membrane-enclosed organelle made up of functionally and structurally distinct domains. The ER domains include the nuclear envelope (NE) and the peripheral ER, which is a network of tubules and sheets spread throughout the cytoplasm. The structural organization of the ER is related to its many different cellular functions. Here we will discuss how the various functional domains of the peripheral ER are organized into structurally distinct domains that exist within the continuous membrane bilayer throughout the cell cycle. In addition, we will summarize our current knowledge on how peripheral ER membranes contact various other regions of the cytoplasm including the cytoskeleton, mitochondria, Golgi, and the plasma membrane and what is known about the functions of these interactions.
Topics: Animals; Biological Transport; COS Cells; Chlorocebus aethiops; Cytoplasm; Cytoskeleton; Endoplasmic Reticulum; Golgi Apparatus; Lipid Bilayers; Mitochondria; Mitosis; Models, Biological; Organelles; Phospholipids; Protein Structure, Tertiary
PubMed: 19447593
DOI: 10.1016/j.ceb.2009.04.004