Research, Research Articles

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.

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Luminal acetylation of microtubules is not essential for Plasmodium berghei and Toxoplasma gondii survival

December 17, 2025

Acetylation of α-tubulin at lysine 40 is not essential for cytoskeletal stability in Plasmodium berghei or Toxoplasma gondii, suggesting redundancy and plasticity in microtubule regulation in these parasites.

The dual-site agonist for human M2 muscarinic receptors Iper-8-naphtalimide induces mitochondrial dysfunction in Saccharomyces cerevisiae

December 12, 2025

S. cerevisiae is a model to study human GPCRs. N-8-Iper, active against glioblastoma via M2 receptor, causes mitochondrial damage in yeast by binding Ste2, highlighting evolutionary conservation of GPCRs.

The core genetic drivers of chronological aging in yeast are universal regulators of longevity

October 31, 2025

This study provides an integrated view of the core genetic landscape underlying aging in yeast, highlighting the value of the chronological lifespan paradigm for investigating conserved mechanisms of aging.

Organelle activity organized by the endoplasmic reticulum-mitochondria encounter structure –ERMES– is essential for Podospora anserina development

September 12, 2025

This study shows that the regulation of the activity of multiple organelles by the ERMES (Endoplasmic Reticulum-Mitochondria Encounter Structure) tethering complex is essential for fungal growth and sexual development.

Role of the putative sit1 gene in normal germination of spores and virulence of the Mucor lusitanicus

August 12, 2025

Mucormycosis is a life-threatening infection caused by certain members of the fungal order Mucorales, with increased incidence in recent years. Individuals with untreated diabetes mellitus, and patients treated with deferoxamine are particularly susceptible to this infection.

Tumor microenvironment signatures enhances lung adenocarcinoma prognosis prediction: Implication of intratumoral microbiota

August 11, 2025

The interaction between intratumoral microbiome and the tumor microenvironment (TME) has furthered our understanding of tumor ecology. Yet, the implications of their interaction for lung cancer management remain unclear.

Persistence phenotype of adherent-invasive Escherichia coli in response to ciprofloxacin, revealing high-persistence strains

July 11, 2025

We investigated the roles of the resident antibiotic resistance plasmid, the stress response protein HtrA, and macrophage-induced persister formation. Our results revealed broad variability in persister cell formation among AIEC strains.

Knocking out histidine ammonia-lyase by using CRISPR-Cas9 abolishes histidine role in the bioenergetics and the life cycle of Trypanosoma cruzi

June 25, 2025

Recent studies have highlighted the importance of this pathway in ATP production, redox balance, and the maintenance of cellular homeostasis in T. cruzi. In this work, we focus on the first step of the histidine degradation pathway, which is performed by the enzyme histidine ammonia lyase. Here we determined the kinetic and biochemical parameters of the T. cruzi histidine ammonia-lyase.

Dissecting the cell cycle regulation, DNA damage sensitivity and lifespan effects of caffeine in fission yeast

June 24, 2025

Our findings show that caffeine accelerates mitotic division and is beneficial for CLS through AMPK. Direct pharmacological targeting of AMPK may serve towards healthspan and lifespan benefits beyond yeasts, given the highly conserved nature of this key regulatory cellular energy sensor.

Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

June 12, 2025

Nitrogen metabolism in Saccharomyces cerevisiae is tightly regulated to optimize the utilization of available nitrogen sources. Uga3 is a known transcription factor involved in the gamma-aminobutyric acid (GABA) pathway; however, its broader role in nitrogen metabolism remains unclear.

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