Research, Research Reports
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
Chen Sun#, Jian Li#, Yu Cao, Gongbo Long and Bing Zhou
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling
Viktor Scheidt1,#, André Jüdes1,#, Christian Bär1,2,#, Roland Klassen1 and Raffael Schaffrath1
The herein presented data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.
Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei
Neta Shlezinger1,#, Elad Eizner1,2,#, Stas Dubinchik2, Anna Minz-Dub1, Rachel Tetroashvili1, Adi Reider1, Amir Sharon1
This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.
Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan
Ivan Orlandi1,2, Damiano Pellegrino Coppola2 and Marina Vai1,2
This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.
Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion
Marizela Delic1,2, Alexandra B. Graf2,3, Gunda Koellensperger1,4, Christina Haberhauer-Troyer1,4, Stephan Hann1,4, Diethard Mattanovich1,2, Brigitte Gasser1,2
This article investigates the role of Yap1 during the production of recombinant secretory proteins in glucose based growth conditions in Pichia pastoris, and reports a novel role of Yap1 during ER-resident oxidative protein folding.
Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature
María López-Malo1,2, Estéfani García-Ríos1, Rosana Chiva1 and José Manuel Guillamon1
This study confirms the importance of specific genes in growth and fermentation activity of Saccharomyces cerevisiae at low temperature.
Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin
Pieter Spincemaille1,+, Gursimran Chandhok2,+, Andree Zibert2, Hartmut Schmidt2, Jef Verbeek3, Patrick Chaltin4,5, Bruno P.A. Cammue1,6,#, David Cassiman3, Karin Thevissen1,#
This study reports the identification of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) and shows that specific ARBs increase yeast tolerance to Cu and Cp, and affect markers of Cu-induced apoptosis. Likewise, this study finds that specific ARBs increase human cell line tolerance to Cu and decrease the prevalence of apoptotic markers.
An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids
Harriet Allison1, Amanda J. O’Reilly1, Jeremy Sternberg2 and Mark C. Field1
This work describes a novel family of type I membrane proteins ("invariant glycoproteins") and proposes them as trypanosomatid-specific ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, that utilise oligomerisation as an ER retention mechanism.
Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program
Cornelia Amariei, Rainer Machné, Viktor Stolc, Tomoyoshi Soga, Masaru Tomita and Douglas B. Murray
Using multiple approaches, this work implies a nucleosome focusing event as a key step that resets transcription during the respiratory oscillation.
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.