Research, Research Articles

Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates

Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates

Steve Brunette1,#, Anupam Sharma1,2,#, Ryan Bell1, Lawrence Puente1 and Lynn A Megeney1,2,3,*

Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.

Metallothionein Cup1 attenuates nitrosative stress in the yeast Saccharomyces cerevisiae

Yuki Yoshikawa1,2,#, Ryo Nasuno1,3,#, Naoki Takaya4 and Hiroshi Takagi1,*

Our findings suggest that the yeast metallothionein Cup1 contributes to nitrosative stress tolerance, possibly as a constitutive rather than an inducible defense mechanism.

GFP fusions of Sec-routed extracellular proteins in Staphylococcus aureus reveal surface-associated coagulase in biofilms

Dominique C. S. Evans1,2,#, Amanda B. Khamas1,#, Lisbeth Marcussen1, Kristian S. Rasmussen3, Janne K. Klitgaard3, Birgitte H. Kallipolitis3, Janni Nielsen1, Daniel E. Otzen1, Mark C. Leake2,4 and Rikke L. Meyer1,5

We show that msfGFP can be used to generate extracellular fluorescent fusion proteins in S. aureus, applicable for proteins that are secreted through the Sec pathway. When fused to coagulase, msfGFP did not hinder the biological function, and the fusion protein localised to the fibrin pseudocapsule surrounding clusters of S. aureus cells.

Atg1, a key regulator of autophagy, functions to promote MAPK activation and cell death upon calcium overload in fission yeast

Teruaki Takasaki1, Ryosuke Utsumi1, Erika Shimada1, Asuka Bamba1, Kanako Hagihara2, Ryosuke Satoh1, and Reiko Sugiura1

Here, we provide evidence that the fission yeast Atg1 regulates cell death responses upon intracellular calcium load in addition to its role in promoting Pmk1 MAPK.

Acetate modulates the inhibitory effect of Lactobacillus gasseri against the pathogenic yeasts Candida albicans and Candida glabrata

Nuno A. Pedro1,2, Gabriela Fontebasso1,2, Sandra N. Pinto1,2, Marta Alves3 and Nuno P. Mira1,2

The results herein described advance the design of new anti-Candida therapies based on probiotics, in particular, those based on vaginal lactobacilli species, helping to reduce the significant burden that infections caused by Candida have today in human health.

D-Serine reduces the expression of the cytopathic genotoxin colibactin

D-Serine reduces the expression of the cytopathic genotoxin colibactin

Jennifer C. Hallam1,#, Sofia Sandalli1,#, Iris Floria1, Natasha C. A. Turner1, Min Tang-Fichaux2, Eric Oswald2,3, Nicky O’Boyle1,4 and Andrew J. Roe1

Sensing and responding to environmental cues and signalling molecules is crucial for bacterial survival. In this study we have identified a D-amino acid that has a strong regulatory effect on the pks genomic island which encodes for biosynthesis genes for the genotoxic compound colibactin.

A modular cloning (MoClo) toolkit for reliable intracellular protein targeting in the yeast Saccharomyces cerevisiae

Pavel Simakin1,#, Christian Koch1,# and Johannes M. Herrmann1

In this study, we describe an advanced Molecular cloning toolkit that is designed for the baker’s yeast Saccharomyces cerevisiae and optimized for the targeting of proteins of interest to specific cellular compartments.

The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes

Alexandr Makarov1, Jakub Began2,†, Ileana Corvo Mautone1,3, Erika Pinto1, Liam Ferguson1, Martin Zoltner1,4, Sebastian Zoll2 and Mark C. Field1,5

By CRISPR/Cas9 knockout and biophysical analysis, we show here that the invariant surface glycoprotein 75 directly binds the the century-old drug suramin and mediates uptake of additional naphthol-related compounds, making this glycoprotein a conduit for entry of at least one structural class of trypanocidal compounds.

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Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production

January 26, 2018

Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. Here, Gamero-Sandemetrio et al. present findings that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after active dry yeast (ADY) production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.

Molecular signature of the imprintosome complex at the mating-type locus in fission yeast

January 16, 2018

Genetic and molecular studies have indicated that an epigenetic imprint at mat1, the sexual locus of fission yeast, initiates mating type switching. Here, Raimondi et al. characterized the recruitment of early players of mating type switching at the mat1 region and suggest a nucleoprotein protective structure defined as imprintosome.

Leishmania guyanensis parasites block the activation of the inflammasome by inhibiting maturation of IL-1β

January 14, 2018

The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses mediated by Toll-Like-Receptor-3 (TLR3). Here, Hartely et al. investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology. They postulate that avoidance of the inflammasome pathways is likely an important mechanism of virulence in Leishmania infection irrespective of the LRV1-status.

A novel system to monitor mitochondrial translation in yeast

January 13, 2018

In this study Suhm et al. present a novel system to monitor mitochondrial translation by detection of mitochondrial GFP-translation through fluorescence microscopy and flow cytometry in functional mitochondria. This novel tool allows the investigation of the function and regulation of mitochondrial translation during stress signaling, aging and mitochondrial biogenesis.

Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

December 28, 2017

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. Saccharomyces cerevisiae has two FITM homologues and the presented results suggest that Scs3p and Yft2p as well as FITMs in general are lipid phosphatase/phosphotransferase (LPT) enzymes involved in an as yet unknown critical step in phospholipid metabolism.

Yeast quiescence exit swiftness is influenced by cell volume and chronological age

December 6, 2017

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here, Laporte et al. explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Overall, their data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.

A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast

December 5, 2017

In this article Avagliano Trezza et al. describe a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker’s yeast) that provides a versatile tool to study complex post-translational modifications in a cellular setting.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae : biophysical mechanisms and implications for acetic acid tolerance

December 1, 2017

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.

Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

November 30, 2017

This article indicates that spartin, a protein linked to hereditary spastic paraplegias, extends yeast lifespan and reduces age-related damage by associating with mitochondria and interacting with key metabolic proteins, implicating energy metabolism in its protective role during aging.

A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis

November 27, 2017

Fingolimod hydrochloride (FTY720) is an immune modulator for multiple sclerosis that also induces cancer cell apoptosis through reactive oxygen species generation, with a new study using fission yeast uncovering a gene network related to ROS homeostasis as a possible mechanism of FTY720's toxicity.

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