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The EMBO Journal Aug 2016Cells contain numerous, molecularly distinct cellular compartments that are not enclosed by lipid bilayers. These compartments are implicated in a wide range of cellular... (Review)
Review
Cells contain numerous, molecularly distinct cellular compartments that are not enclosed by lipid bilayers. These compartments are implicated in a wide range of cellular activities, and they have been variously described as bodies, granules, or organelles. Recent evidence suggests that a liquid-liquid phase separation (LLPS) process may drive their formation, possibly justifying the unifying term "droplet organelle". A veritable deluge of recent publications points to the importance of low-complexity proteins and RNA in determining the physical properties of phase-separated structures. Many of the proteins linked to such structures are implicated in human diseases, such as amyotrophic lateral sclerosis (ALS). We provide an overview of the organizational principles that characterize putative "droplet organelles" in healthy and diseased cells, connecting protein biochemistry with cell physiology.
Topics: Cell Physiological Phenomena; Cytosol; Macromolecular Substances; Multienzyme Complexes
PubMed: 27357569
DOI: 10.15252/embj.201593517 -
Cellular Microbiology Apr 2021
Topics: Animals; Bacteria; Cell Membrane; Cytosol; Immunity, Innate; Parasites; Phagocytes
PubMed: 33305902
DOI: 10.1111/cmi.13296 -
Advances in Experimental Medicine and... 2020Measuring free Ca concentration ([Ca]) in the cytosol or organelles is routine in many fields of research. The availability of membrane permeant forms of indicators... (Review)
Review
Measuring free Ca concentration ([Ca]) in the cytosol or organelles is routine in many fields of research. The availability of membrane permeant forms of indicators coupled with the relative ease of transfecting cell lines with biological Ca sensors have led to the situation where cellular and subcellular [Ca] is examined by many non-specialists. In this chapter, we evaluate the most used Ca indicators and highlight what their major advantages and disadvantages are. We stress the potential pitfalls of non-ratiometric techniques for measuring Ca and the clear advantages of ratiometric methods. Likely improvements and new directions for Ca measurement are discussed.
Topics: Animals; Calcium; Cytological Techniques; Cytosol; Humans; Organelles
PubMed: 31646505
DOI: 10.1007/978-3-030-12457-1_2 -
Current Opinion in Virology Feb 2017The ability to recognize invading viral pathogens and to distinguish their components from those of the host cell is critical to initiate the innate immune response. The... (Review)
Review
The ability to recognize invading viral pathogens and to distinguish their components from those of the host cell is critical to initiate the innate immune response. The efficiency of this detection is an important factor in determining the susceptibility of the cell to viral infection. Innate sensing of viruses is, therefore, an indispensable step in the line of defense for cells and organisms. Recent discoveries have uncovered novel sensors of viral components and hallmarks of infection, as well as mechanisms by which cells discriminate between self and non-self. This review highlights the mechanisms used by cells to detect viral pathogens in the cytosol, and recent advances in the field of cytosolic sensing of viruses.
Topics: Animals; Cytosol; Humans; Immunity, Innate; Receptors, Immunologic; Viruses
PubMed: 27951430
DOI: 10.1016/j.coviro.2016.11.012 -
Nucleosides, Nucleotides & Nucleic Acids 2022cN-II is a cytosolic 5'-nucleotidase with preference for IMP and GMP over AMP. The enzyme has been extensively studied over the last 20-30 years both for its enzymatic... (Review)
Review
cN-II is a cytosolic 5'-nucleotidase with preference for IMP and GMP over AMP. The enzyme has been extensively studied over the last 20-30 years both for its enzymatic activity, structure, role in nucleotide metabolism and in cell biology, as well as in diseases. With the aim of highlighting the complexity of the enzyme, I will, as during PP21, present work from our group and others working on cN-II and its various roles and not give an exhaustive overview of new data.
Topics: 5'-Nucleotidase; Cytosol
PubMed: 34612808
DOI: 10.1080/15257770.2021.1983828 -
International Review of Cell and... 2014Diffusion is the basic mode of transport for molecules in living cells. Diffusion leads to dispersion of individual molecules, but it is also the driving force behind... (Review)
Review
Diffusion is the basic mode of transport for molecules in living cells. Diffusion leads to dispersion of individual molecules, but it is also the driving force behind biochemical reactions and pattern formation as diffusional motion mediates reactant encounters. Owing to macromolecular crowding in all cellular fluids and biomembranes, diffusion of molecules in cells is quite different from the motion observed in dilute solutions in a test tube. Hindered and anomalous diffusion are seen in cells, and biochemical reactions are affected by these. This review is intended to give an introduction and a brief overview about causes and consequences of crowding-induced diffusion anomalies and their impact on biochemical reactions.
Topics: Animals; Biological Transport, Active; Cell Membrane; Cytosol; Humans; Models, Biological
PubMed: 24380600
DOI: 10.1016/B978-0-12-800046-5.00011-4 -
Current Pharmaceutical Biotechnology Jun 2008Immunotoxins are chimeric molecules that specifically target tumor cells, as they are made up of toxins linked to an antibody directed to a specific, cell-surface... (Review)
Review
Immunotoxins are chimeric molecules that specifically target tumor cells, as they are made up of toxins linked to an antibody directed to a specific, cell-surface tumor-associated-antigen (TAA). When the immune moiety is internalized by the tumor cell, it will carry the conjugated toxin into the cell, so that the cell will be selectively killed in a way postulated more than a hundred years ago by Paul Ehrlich, the first author to use the term magic bullet. To date, toxicity and immunogenicity have complicated the clinical use of most immunotoxins. More recently, based on the immunotoxin principle, immunoRNases have been proposed, in which the toxin moiety of immunotoxins is replaced by a non-toxic RNase. An immunoRNase (IR) is in fact an immuno-pro-toxin, as it can travel in the bloodstream without any damages to cells devoid of the targeted TAA, while magically selecting the cells targeted by the immune moiety. Once internalized, the RNase moiety will exert its RNA degrading activity, which will readily lead to the death of the targeted cell. By choosing a human RNase, and a human antibody fragment as immune moiety, an IR would be not only non-toxic, but also non-immunogenic. As for the possible inhibitory action of the cytosolic RNase inhibitor, exerted on all non-toxic vertebrate RNases, it can be opposed by flooding the cytosol with high levels of IR, which will neutralize the RNase inhibitor, or by using RNases resistant to the inhibitor.
Topics: Animals; Antigens, Neoplasm; Cytosol; Humans; Immunotherapy; Immunotoxins; Models, Molecular; Neoplasms; Protein Binding; Recombinant Fusion Proteins; Ribonucleases
PubMed: 18673286
DOI: 10.2174/138920108784567254 -
Current Medicinal Chemistry 2013Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of... (Review)
Review
Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology.
Topics: 5'-Nucleotidase; Animals; Brain; Cytosol; Energy Metabolism; Humans; Ischemia
PubMed: 23992316
DOI: 10.2174/0929867311320340002 -
Traffic (Copenhagen, Denmark) Oct 2015Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is... (Review)
Review
Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is particularly critical in fast-growing tumour cells. Thus, the process can serve as target both for potential cancer drugs and for bacterial virulence factors. Inhibitors of protein transport across the ER membrane range from broad-spectrum to highly substrate-specific and can interfere with virtually any stage of this multistep process, and even with transport of endocytosed antigens into the cytosol for cross-presentation.
Topics: Animals; Antineoplastic Agents; Cytosol; Endoplasmic Reticulum; Humans; Membrane Transport Proteins; Protein Transport
PubMed: 26122014
DOI: 10.1111/tra.12308 -
Dalton Transactions (Cambridge, England... Mar 2013The nature of the cytosolic iron pool remains largely uncharacterized, although a range of candidate ligands and chaperones have been proposed. Herein an overview is... (Review)
Review
The nature of the cytosolic iron pool remains largely uncharacterized, although a range of candidate ligands and chaperones have been proposed. Herein an overview is presented of cytosolic non heme and non iron-sulphur cluster protein iron binding sites and the influence of ligands on the redox activity of iron. This analysis leads to the concept of iron(II) glutathione functioning as the labile cytosolic iron pool and offers a means for the selection of iron over manganese in subsequent incorporation into a wide range of iron-dependent enzymes and electron transfer proteins. Glutathione and glutathione-binding glutaredoxins play a critical role in iron sulfur cluster synthesis and Fe(II)GS (iron(II) coordinated by the thiol function of glutathione) is a suitable iron donor for this biosynthetic route. Significantly, both glutathione and glutaredoxins are universally distributed and thus a controlling influence of glutathione on intracellular iron trafficking is likely to be a common feature of the majority of living organisms.
Topics: Animals; Cytosol; Humans; Iron; Mitochondria; Molecular Chaperones; Oxidation-Reduction; Sulfur
PubMed: 23232973
DOI: 10.1039/c2dt32149a