Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: The Journal of biological chemistry, 03 June 2011, Vol.286(22), pp.19958-72
    Description: Pathological neuronal inclusions of the 43-kDa TAR DNA-binding protein (TDP-43) are implicated in dementia and motor neuron disorders; however, the molecular mechanisms of the underlying cell loss remain poorly understood. Here we used a yeast model to elucidate cell death mechanisms upon expression of human TDP-43. TDP-43-expressing cells displayed markedly increased markers of oxidative stress, apoptosis, and necrosis. Cytotoxicity was dose- and age-dependent and was potentiated upon expression of disease-associated variants. TDP-43 was localized in perimitochondrial aggregate-like foci, which correlated with cytotoxicity. Although the deleterious effects of TDP-43 were significantly decreased in cells lacking functional mitochondria, cell death depended neither on the mitochondrial cell death proteins apoptosis-inducing factor, endonuclease G, and cytochrome c nor on the activity of cell death proteases like the yeast caspase 1. In contrast, impairment of the respiratory chain attenuated the lethality upon TDP-43 expression with a stringent correlation between cytotoxicity and the degree of respiratory capacity or mitochondrial DNA stability. Consistently, an increase in the respiratory capacity of yeast resulted in enhanced TDP-43-triggered cytotoxicity, oxidative stress, and cell death markers. These data demonstrate that mitochondria and oxidative stress are important to TDP-43-triggered cell death in yeast and may suggest a similar role in human TDP-43 pathologies.
    Keywords: Oxidative Stress ; DNA, Fungal -- Metabolism ; DNA, Mitochondrial -- Metabolism ; DNA-Binding Proteins -- Biosynthesis ; Mitochondria -- Metabolism ; Recombinant Proteins -- Biosynthesis ; Saccharomyces Cerevisiae -- Metabolism ; Tdp-43 Proteinopathies -- Metabolism
    ISSN: 00219258
    E-ISSN: 1083-351X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 29 May 2012, Vol.109(22), pp.8658-63
    Description: The large protein superfamily of NADPH oxidases (NOX enzymes) is found in members of all eukaryotic kingdoms: animals, plants, fungi, and protists. The physiological functions of these NOX enzymes range from defense to specialized oxidative biosynthesis and to signaling. In filamentous fungi, NOX enzymes are involved in signaling cell differentiation, in particular in the formation of fruiting bodies. On the basis of bioinformatics analysis, until now it was believed that the genomes of unicellular fungi like Saccharomyces cerevisiae and Schizosaccharomyces pombe do not harbor genes coding for NOX enzymes. Nevertheless, the genome of S. cerevisiae contains nine ORFs showing sequence similarity to the catalytic subunits of mammalian NOX enzymes, only some of which have been functionally assigned as ferric reductases involved in iron ion transport. Here we show that one of the nine ORFs (YGL160W, AIM14) encodes a genuine NADPH oxidase, which is located in the endoplasmic reticulum (ER) and produces superoxide in a NADPH-dependent fashion. We renamed this ORF YNO1 (yeast NADPH oxidase 1). Overexpression of YNO1 causes YCA1-dependent apoptosis, whereas deletion of the gene makes cells less sensitive to apoptotic stimuli. Several independent lines of evidence point to regulation of the actin cytoskeleton by reactive oxygen species (ROS) produced by Yno1p.
    Keywords: Apoptosis ; Actins -- Metabolism ; Nadph Oxidases -- Metabolism ; Reactive Oxygen Species -- Metabolism ; Saccharomyces Cerevisiae -- Metabolism ; Saccharomyces Cerevisiae Proteins -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Nucleic acids research, 28 September 2018, Vol.46(17), pp.9201-9219
    Description: The dissemination of multi-resistant bacteria represents an enormous burden on modern healthcare. Plasmid-borne conjugative transfer is the most prevalent mechanism, requiring a type IV secretion system that enables bacteria to spread beneficial traits, such as resistance to last-line antibiotics, among different genera. Inc18 plasmids, like the Gram-positive broad host-range plasmid pIP501, are substantially involved in propagation of vancomycin resistance from Enterococci to methicillin-resistant strains of Staphylococcus aureus. Here, we identified the small cytosolic protein TraN as a repressor of the pIP501-encoded conjugative transfer system, since deletion of traN resulted in upregulation of transfer factors, leading to highly enhanced conjugative transfer. Furthermore, we report the complex structure of TraN with DNA and define the exact sequence of its binding motif. Targeting this protein-DNA interaction might represent a novel therapeutic approach against the spreading of antibiotic resistances.
    Keywords: Conjugation, Genetic ; Bacterial Outer Membrane Proteins -- Chemistry ; DNA, Bacterial -- Chemistry ; Enterococcus Faecalis -- Genetics ; Escherichia Coli Proteins -- Chemistry ; Plasmids -- Chemistry ; Type IV Secretion Systems -- Genetics
    ISSN: 03051048
    E-ISSN: 1362-4962
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Cell Cycle, 03 August 2015, Vol.14(15), pp.2389-2390
    Keywords: Biology
    ISSN: 1538-4101
    E-ISSN: 1551-4005
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 2012, Vol.109(22), pp.8658-8663
    Description: The large protein superfamily of NADPH oxidases (NOX enzymes) is found in members of all eukaryotic kingdoms: animals, plants, fungi, and protists. The physiological functions of these NOX enzymes range from defense to specialized oxidative biosynthesis and to signaling. In filamentous fungi, NOX enzymes are involved in signaling cell differentiation, in particular in the formation of fruiting bodies. On the basis of bioinformatics analysis, until now it was believed that the genomes of unicellular fungi like Saccharomyces cerevisiae and Schizosaccharomyces pombe do not harbor genes coding for NOX enzymes. Nevertheless, the genome of S. cerevisiae contains nine ORFs showing sequence similarity to the catalytic subunits of mammalian NOX enzymes, only some of which have been functionally assigned as ferric reductases involved in iron ion transport. Here we show that one of the nine ORFs (YGL160W, AIM14) encodes a genuine NADPH oxidase, which is located in the endoplasmic reticulum (ER) and produces superoxide in a NADPH-dependent fashion. We renamed this ORF YNO1 (yeast NADPH oxidase 1). Overexpression of YNO1 causes YCA1-dependent apoptosis, whereas deletion of the gene makes cells less sensitive to apoptotic stimuli. Several independent lines of evidence point to regulation of the actin cytoskeleton by reactive oxygen species (ROS) produced by Yno1p. ; p. 8658-8663.
    Keywords: Nadp (Coenzyme) ; Open Reading Frames ; Animals ; Actin ; Apoptosis ; Reactive Oxygen Species ; Genes ; Endoplasmic Reticulum ; Gene Overexpression ; Enzymes ; Fruiting Bodies ; Saccharomyces Cerevisiae ; Gene Deletion ; Microfilaments ; Ion Transport ; Yeasts ; Bioinformatics ; Cell Differentiation ; Biosynthesis ; Protein Subunits ; Schizosaccharomyces Pombe
    ISSN: 0027-8424
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Oxidative Medicine and Cellular Longevity, 2018, Vol.2018, 2 pages
    Description: [...]due to the high conservation of RCD-related cellular processes, yeast can be used to study human pathologies caused by deviations in RCD. [...]the analysis of cell death routes solely present/induced in yeast and other fungi might point to novel therapeutic strategies to combat fungal infections. An analysis of yeast cells harbouring differing genome copy numbers, ranging from haploid to tetraploid, provides evidence for a correlation between an increase in cell volume achieved via additional genome copies and the reproductive as well as the postreproductive lifespan. Besides that, analysis of adaptive stress strategies or tolerance mechanisms elicited by different organisms under RCD stress or oxidative stress in general is of great interest. [...]this special issue will provide more insights into RCD and into tolerance mechanisms elicited in cells experiencing RCD.
    Keywords: Fungi ; Homeostasis ; Aging ; Cancer Therapies ; Colonies & Territories ; Deoxyribonucleic Acid–DNA ; Fungal Infections ; Autophagy ; Genomes ; Metabolism ; Yeast ; Apoptosis ; Kinases ; Oxidative Stress;
    ISSN: 1942-0900
    E-ISSN: 1942-0994
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: PLoS ONE, 2010, Vol.5(10)
    Description: Background Parkinson's disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by α-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. Methodology/Principal Findings We expressed wild-type synphilin-1 or its R621C mutant either alone or in combination with α-synuclein in the yeast Saccharomyces cerevisiae and monitored the intracellular localization and inclusion formation of the proteins as well as the repercussions on growth, oxidative stress and cell death. We found that wild-type and mutant synphilin-1 formed inclusions and accelerated inclusion formation by α-synuclein in yeast cells, the latter being correlated to enhanced phosphorylation of serine-129. Synphilin-1 inclusions co-localized with lipid droplets and endomembranes. Consistently, we found that wild-type and mutant synphilin-1 interacts with detergent-resistant membrane domains, known as lipid rafts. The expression of synphilin-1 did not incite a marked growth defect in exponential cultures, which is likely due to the formation of aggresomes and the retrograde transport of inclusions from the daughter cells back to the mother cells. However, when the cultures approached stationary phase and during subsequent ageing of the yeast cells, both wild-type and mutant synphilin-1 reduced survival and triggered apoptotic and necrotic cell death, albeit to a different extent. Most interestingly, synphilin-1 did not trigger cytotoxicity in ageing cells lacking the sirtuin Sir2. This indicates that the expression of synphilin-1 in wild-type cells causes the deregulation of Sir2-dependent processes, such as the maintenance of the autophagic flux in response to nutrient starvation. Conclusions/Significance Our findings demonstrate that wild-type and mutant synphilin-1 are lipid raft interacting proteins that form inclusions and accelerate inclusion formation of α-synuclein when expressed in yeast. Synphilin-1 thereby induces cytotoxicity, an effect most pronounced for the wild-type protein and mediated via Sir2-dependent processes.
    Keywords: Research Article ; Molecular Biology ; Cell Biology/Cellular Death And Stress Responses ; Cell Biology/Membranes And Sorting ; Neuroscience/Neurobiology Of Disease And Regeneration
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Yeast, August 2014, Vol.31(8), pp.289-298
    Description: The identification and characterization of the molecular determinants governing ageing represents the key to counteracting age‐related diseases and eventually prolonging our health span. A large number of fundamental insights into the ageing process have been provided by research into the budding yeast , which couples a wide array of technical advantages with a high degree of genetic, proteomic and mechanistic conservation. Indeed, this unicellular organism harbours regulatory pathways, such as those related to programmed cell death or nutrient signalling, that are crucial for ageing control and are reminiscent of other eukaryotes, including mammals. Here, we summarize and discuss three different paradigms of yeast ageing: replicative, chronological and colony ageing. We address their physiological relevance as well as the specific and common characteristics and regulators involved, providing an overview of the network underlying ageing in one of the most important eukaryotic model organisms. © 2014 The Authors. published by John Wiley & Sons Ltd. This review discusses the three paradigms of yeast ageing: replicative, chronological and colony ageing. Programmed cell death (PCD) of replicatively old mother cells, chronologically aged cells and cells in the colony centre is accompanied by overproduction of reactive oxygen species (ROS). This death of individual cells ensures adaptation to the changing environment and long‐term survival of the clonal population.
    Keywords: Programmed Cell Death ; Apoptosis ; Necrosis ; Ageing ; Replicative Lifespan ; Chronological Lifespan ; Yeast ; Altruism ; Adaptation ; Colony Differentiation
    ISSN: 0749-503X
    E-ISSN: 1097-0061
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Neural Regeneration Research, 2017, Vol.12(11), pp.1776-1779
    Description: Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades....
    Keywords: Natural Sciences ; Biological Sciences ; Naturvetenskap ; Biologiska Vetenskaper ; Medical And Health Sciences ; Basic Medicine ; Medicin Och Hälsovetenskap ; Medicinska Och Farmaceutiska Grundvetenskaper ; Neurodegeneration ; Parkinson'S Disease ; Alpha-Synuclein ; Cathepsin D ; Calcineurin ; Retromer ; Yeast ; Lysosome ; Endosomal Sorting
    ISSN: 1673-5374
    E-ISSN: 18767958
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Oxidative Medicine and Cellular Longevity, 2018, Vol.2018
    Description: The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist...
    Keywords: Natural Sciences ; Biological Sciences ; Naturvetenskap ; Biologiska Vetenskaper
    ISSN: 1942-0900
    E-ISSN: 19420994
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages