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Biochimica Et Biophysica Acta Feb 2013Chloroplasts are unique organelles that are responsible for photosynthesis. Although chloroplasts contain their own genome, the majority of chloroplast proteins are... (Review)
Review
Chloroplasts are unique organelles that are responsible for photosynthesis. Although chloroplasts contain their own genome, the majority of chloroplast proteins are encoded by the nuclear genome. These proteins are transported to the chloroplasts after translation in the cytosol. Chloroplasts contain three membrane systems (outer/inner envelope and thylakoid membranes) that subdivide the interior into three soluble compartments known as the intermembrane space, stroma, and thylakoid lumen. Several targeting mechanisms are required to deliver proteins to the correct chloroplast membrane or soluble compartment. These mechanisms have been extensively studied using purified chloroplasts in vitro. Prior to targeting these proteins to the various compartments of the chloroplast, they must be correctly sorted in the cytosol. To date, it is not clear how these proteins are sorted in the cytosol and then targeted to the chloroplasts. Recently, the cytosolic carrier protein AKR2 and its associated cofactor Hsp17.8 for outer envelope membrane proteins of chloroplasts were identified. Additionally, a mechanism for controlling unimported plastid precursors in the cytosol has been discovered. This review will mainly focus on recent findings concerning the possible cytosolic events that occur prior to protein targeting to the chloroplasts. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.
Topics: Cell Membrane; Chloroplasts; Cytosol; Photosynthesis; Plant Proteins; Protein Transport
PubMed: 22450030
DOI: 10.1016/j.bbamcr.2012.03.006 -
Cellular Microbiology Oct 2017Listeria monocytogenes, the causative agent of listeriosis, is an intracellular pathogen that is exquisitely evolved to survive and replicate in the cytosol of... (Review)
Review
Listeria monocytogenes, the causative agent of listeriosis, is an intracellular pathogen that is exquisitely evolved to survive and replicate in the cytosol of eukaryotic cells. Eukaryotic cells typically restrict bacteria from colonising the cytosol, likely through a combination of cell autonomous defences, nutritional immunity, and innate immune responses including induction of programmed cell death. This suggests that L. monocytogenes and other professional cytosolic pathogens possess unique metabolic adaptations, not only to support replication but also to facilitate resistance to host-derived stresses/defences and avoidance of innate immune activation. In this review, we outline our current understanding of L. monocytogenes metabolism in the host cytosol and highlight major metabolic processes which promote intracellular replication and survival.
Topics: Cytosol; Immunity, Innate; Listeria monocytogenes; Virulence
PubMed: 28656691
DOI: 10.1111/cmi.12762 -
Cerebellum (London, England) Sep 2012Cerebellar Purkinje neurons receive synaptic inputs from three different sources: the excitatory parallel fibre and climbing fibre synapses as well as the inhibitory... (Review)
Review
Cerebellar Purkinje neurons receive synaptic inputs from three different sources: the excitatory parallel fibre and climbing fibre synapses as well as the inhibitory synapses from molecular layer stellate and basket cells. These three synaptic systems use distinct mechanisms in order to generate Ca(2+) signals that are specialized for specific modes of neurotransmitter release and post-synaptic signal integration. In this review, we first describe the repertoire of Ca(2+) regulatory mechanisms that generate and regulate the amplitude and timing of Ca(2+) fluxes during synaptic transmission and then explore how these mechanisms interact to generate the unique functional properties of each of the Purkinje neuron synapses.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Cell Membrane; Cerebellum; Cytosol; Humans; Purkinje Cells; Sodium-Calcium Exchanger; Synapses; Synaptic Transmission
PubMed: 20596808
DOI: 10.1007/s12311-010-0185-6 -
Drug Metabolism Reviews Feb 2013The cytosolic sulfotransferases (SULTs) are a multigene family of enzymes that catalyze the transfer of a sulfonate group from the physiologic sulfate donor,... (Review)
Review
The cytosolic sulfotransferases (SULTs) are a multigene family of enzymes that catalyze the transfer of a sulfonate group from the physiologic sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate, to a nucleophilic substrate to generate a polar product that is more amenable to elimination from the body. As catalysts of both xenobiotic and endogenous metabolism, the SULTs are major points of contact between the external and physiological environments, and modulation of SULT-catalyzed metabolism can not only affect xenobiotic disposition, but it can also alter endogenous metabolic processes. Therefore, it is not surprising that SULT expression is regulated by numerous members of the nuclear receptor (NR) superfamily that function as sensors of xenobiotics as well as endogenous molecules, such as fatty acids, bile acids, and oxysterols. These NRs include the peroxisome proliferator-activated receptors, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, liver X receptors, farnesoid X receptor, retinoid-related orphan receptors, and estrogen-related receptors. This review summarizes current information about NR regulation of SULT expression. Because species differences in SULT subfamily composition and tissue-, sex-, development-, and inducer-dependent regulation are prominent, these differences will be emphasized throughout the review. In addition, because of the central role of the SULTs in cellular physiology, the effect of NR-mediated SULT regulation on physiological and pathophysiological processes will be discussed. Gaps in current knowledge that require further investigation are also highlighted.
Topics: Animals; Cytosol; Humans; Receptors, Cytoplasmic and Nuclear; Sulfotransferases; Xenobiotics
PubMed: 23330539
DOI: 10.3109/03602532.2012.748794 -
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 -
Angewandte Chemie (International Ed. in... Jun 2021Macromolecular drugs inefficiently cross membranes to reach their cytosolic targets. They require drug delivery vectors to facilitate their translocation across the...
Macromolecular drugs inefficiently cross membranes to reach their cytosolic targets. They require drug delivery vectors to facilitate their translocation across the plasma membrane or escape from endosomes. Optimization of these vectors has however been hindered by the difficulty to accurately measure cytosolic arrival. We have developed an exceptionally sensitive and robust assay for the relative or absolute quantification of this step. The assay is based on benzylguanine and biotin modifications on a drug delivery vector of interest, which allow, respectively, for selective covalent capture in the cytosol with a SNAP-tag fusion protein and for quantification at picomolar sensitivity. The assay was validated by determining the absolute numbers of cytosolic molecules for two drug delivery vectors: the B-subunit of Shiga toxin and the cell-penetrating peptide TAT. We expect this assay to favor delivery vector optimization and the understanding of the enigmatic translocation process.
Topics: Cell-Penetrating Peptides; Cytosol; Drug Carriers; Drug Delivery Systems; Humans; Shiga Toxin
PubMed: 33904231
DOI: 10.1002/anie.202102332 -
Current Opinion in Cell Biology Aug 2010The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins that together make up about one third of the cellular proteome. Cells... (Review)
Review
The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins that together make up about one third of the cellular proteome. Cells carefully control the synthetic output of this organelle to regulate both quality and quantity of proteins that emerge. Here, we synthesize current concepts underlying the pathways that mediate protein degradation from the ER and their deployment under physiologic and pathologic conditions.
Topics: Animals; Cytosol; Endoplasmic Reticulum; Humans; Metabolic Networks and Pathways; Protein Processing, Post-Translational; Stress, Physiological
PubMed: 20570125
DOI: 10.1016/j.ceb.2010.05.005 -
Cellular and Molecular Life Sciences :... Mar 1997To examine the role of metallothionein (MT) on heavy metal accumulation in hepatic cytosol of rats, this study was carried out to determine the relative Zn, Cd and...
To examine the role of metallothionein (MT) on heavy metal accumulation in hepatic cytosol of rats, this study was carried out to determine the relative Zn, Cd and Cu-binding capacities of MT in hepatic cytosol of Zn, Cd and Cu-injected rats, respectively. The heavy metal contents were detected in the liver and cytosol in the following proportions: 65.2-74.8% of the Zn content, 61.9-65.6% of the Cu content, and approx. 65% of the Cd content. Each rat was given a single intraperitoneal injection of saline, ZnSO4 (1, 5, 10 and 20 mg Zn/kg b.w.), CuSO4 (2, 4 and 6 mg Cu/kg b.w.) or CdCl2 (1, 2 and 3 mg Cd/kg b.w.). The amounts of the increased Zn and Cu were attributable to MT and high molecular weight proteins, while most of the increased Cd was attributable to MT. There was a close relationship between heavy metal content of the cytosol and MT in all heavy metal-injected rats. Our data demonstrated that approx. 60% of the increased Zn or Cu in the hepatic cytosol of Zn or Cu-injected rats was bound to MT, while 83% of the increased Cd in hepatic cytosol of Cd-injected rats was bound to MT. Therefore the order of relative binding capacity in vivo of MT determined for several metals (Cd > Zn > Cu) did not correlate with the published in vitro order of affinity to MT, Cu > Cd > Zn. These results suggested that the role of MT in Zn or Cu accumulation in the liver of Zn or Cu-injected rats was different from that of MT in Cd accumulation in the liver of Cd-injected rats.
Topics: Animals; Cadmium; Copper; Cytosol; Liver; Male; Metallothionein; Rats; Rats, Sprague-Dawley; Zinc
PubMed: 9104490
DOI: 10.1007/pl00000602 -
Current Pharmaceutical Biotechnology Jun 2008Onconase (ONC) is an amphibian member of the bovine pancreatic ribonuclease (RNase A) superfamily that exhibits innate antitumoral activity. ONC has been granted both... (Review)
Review
Onconase (ONC) is an amphibian member of the bovine pancreatic ribonuclease (RNase A) superfamily that exhibits innate antitumoral activity. ONC has been granted both orphan-drug and fast-track status by the U.S. Food and Drug Administration for the treatment of malignant mesothelioma, and is poised to become the first chemotherapeutic agent based on a ribonuclease. Investigations into the mechanism of ribonuclease-based cytotoxicity have elucidated several important determinants for cytotoxicity, including efficient deliverance of ribonucleolytic activity to the cytosol and preservation of conformation stability. Nevertheless, the most striking similarity between ONC and bovine seminal ribonuclease, another naturally cytotoxic ribonuclease, is their insensitivity to inhibition by the potent cytosolic ribonuclease inhibitor protein (RI). RI typically binds to its ribonuclease ligands with femtomolar affinity--an extraordinary feat considering the modest sequence identity among the bound ribonucleases. Mammalian ribonucleases such as RNase A or its human homologue, RNase 1, have the potential to be more attractive chemotherapeutic agents than ONC owing to their higher catalytic activity, low potential for immunogenicity, favorable tissue distribution, and high therapeutic index, but are limited by their sensitivity to RI. These non-toxic mammalian ribonucleases can be transformed into potent cytotoxins by engendering them with RI-evasion using protein engineering strategies such as site-directed mutagenesis, multimerization, fusion to a targeting moiety, and chemical modification. In several instances, these engineered ribonucleases exhibit greater cytotoxicity in vitro than does ONC. Herein, we review the biochemical characteristics of RIribonuclease complexes and progress towards the development of mammalian ribonuclease-based chemotherapeutics through the elicitation of RI-evasion.
Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Cytosol; Enzyme Stability; Humans; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Binding; Ribonucleases; Sequence Alignment
PubMed: 18673284
DOI: 10.2174/138920108784567344 -
STAR Protocols Mar 2022DNA damage caused by genetic instability or extrinsic treatment can induce DNA leakage from the nucleus or mitochondria into the cytosol and activate innate and adaptive...
DNA damage caused by genetic instability or extrinsic treatment can induce DNA leakage from the nucleus or mitochondria into the cytosol and activate innate and adaptive immunity. To enable characterization of these endogenous cytosolic DNAs and the mechanisms that produce them, we developed an approach for isolation of cytosolic DNA with no detectable mitochondrial contamination. Here we describe cytosolic compartment separation followed by DNA purification from colorectal cancer cells and illustrate how this may be expanded to other cell types.
Topics: Cell Line; Cells, Cultured; Cytosol; DNA; Mitochondria
PubMed: 35535161
DOI: 10.1016/j.xpro.2022.101165