Research, Research Reports

Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK

Nazif Maqani1,#, Ryan D. Fine1,#, Mehreen Shahid1, Mingguang Li1,2, Elisa Enriquez-Hesles1 and Jeffrey S. Smith1

Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Here, Magani et al. identified specific downstream SNF1 targets responsible for CLS extension during CR.

Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells

Maxence de Taffin de Tilques1,$, Jean-Paul Lasserre1,$, François Godard1, Elodie Sardin1, Marine Bouhier1, Marina Le Guedard2,3, Roza Kucharczyk4, Patrice X. Petit5, Eric Testet2, Jean-Paul di Rago1, Déborah Tribouillard-Tanvier1,#

Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). Here, de Taffin de Tilques et al. describe that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of Barth Syndrome (BTHS) and identifies cytosolic translation as a potential therapeutic target for the treatment of this disease.

Production of poly-β-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces

Dino van Dissel1, Joost Willemse1, Boris Zacchetti1, Dennis Claessen1, Gerald B. Pier2, Gilles P. van Wezel1

In this article van Dissel et al. describe new insights to allow better control of liquid-culture morphology of streptomycetes, which may be harnessed to improve growth and industrial exploitation of these highly versatile natural product and enzyme producers.

Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging

Nadia G Rampello1, Maria Stenger2, Benedikt Westermann2, Heinz D Osiewacz1

In aerobic organisms, mitochondrial F1Fo-ATP-synthase is the major site of ATP production. Here, Rampello et al. report on the role of the two dimer assembly factors PaATPE and PaATPG of the aging model Podospora anserina validating a model that links mitochondrial membrane remodeling to aging and identify specific molecular components triggering this process.

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

Esther Gamero-Sandemetrio1, Lucía Payá-Tormo1, Rocío Gómez-Pastor1,3, Agustín Aranda1,2 and Emilia Matallana1,2

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

Célia Raimondi1, Bernd Jagla2, Caroline Proux3, Hervé Waxin4, Serge Gangloff1, Benoit Arcangioli1

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

Mary-Anne Hartley1,¶, Remzi O. Eren1,¶, Matteo Rossi1, Florence Prevel1, Patrik Castiglioni1, Nathalie Isorce1, Chantal Desponds1, Lon-Fye Lye2, Stephen M. Beverley2, Stefan K. Drexler1,&, Nicolas Fasel1,&

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

Tamara Suhm1, Lukas Habernig2, Magdalena Rzepka1, Jayasankar Mohanakrishnan Kaimal3, Claes Andréasson3, Sabrina Büttner2,3 and Martin Ott1

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

Matthew J Hayes1, Vineet Choudhary2, Namrata Ojha2, John JH Shin3, Gil-Soo Han4, George M. Carman4, Christopher JR Loewen3, William A Prinz2 and Timothy P Levine1

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.

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A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus

December 23, 2020

The herein presented results show a BMP-like receptor-regulated SMAD in Haemonchus contortus that is required for larval differentiation and underscore an adaptive functional repurposing of BMP-signaling in parasitic worms.

Nutrient sensing and cAMP signaling in yeast: G-protein coupled receptor versus transceptor activation of PKA

October 12, 2020

The herein presented work supports a model, in which nutrient transceptors are evolutionary ancestors of GPCRs, employing a more primitive direct signaling mechanism compared to the indirect cAMP second-messenger signaling mechanism used by GPCRs for activation of PKA.

Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts

August 10, 2020

In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.

Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast

July 20, 2020

RAD52 is a key protein in DNA repair and suppresses DNA damage in yeast; however, certain variants affecting BRCA2 mutations fail to correct HRR defects. This suggests that HsRAD52 aids multiple DNA repair mechanisms and could be targeted for use in treating BRCA2-deficient cancers.

Systematic analysis of nuclear gene function in respiratory growth and expression of the mitochondrial genome in S. cerevisiae

June 30, 2020

Using yeast Saccharomyces cerevisiae, the authors identified 254 nuclear genes essential for respiratory growth and 12 required for viability without mtDNA. They also found 176 genes involved in mitochondrial protein synthesis and mtDNA maintenance, offering a comprehensive view of the processes supporting oxidative phosphorylation.

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage

April 24, 2020

This study reveals that conserved residues H3E73 and H4E53 in histones H3 and H4 play a crucial role in maintaining genome stability. Mutations at these sites increase recombinogenic DNA damage, likely due to replication-associated issues rather than transcriptional activity, highlighting their importance in DNA damage prevention and repair.

Sulforaphane alters the acidification of the yeast vacuole

March 20, 2020

This study identifies vacuolar pH regulation as a key factor in sulforaphane (SFN) sensitivity, showing that SFN-induced cell death in yeast - and potentially in human cancer cells - is linked to its ability to raise vacuolar or lysosomal pH.

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids

March 12, 2020

This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.

Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae

February 5, 2020

This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.

The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast

January 3, 2020

This study reveals that the loss of heterochromatin silencing in Set2-deficient cells is due to unrestrained Mst2C activity, highlighting the need for spatially restricted chromatin-modifying enzymes to maintain distinct chromatin states.

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