Research, Research Articles

The translationally controlled tumor protein TCTP is involved in cell cycle progression and heat stress response in the bloodstream form of Trypanosoma brucei

Borka Jojic1, Simona Amodeo1,2 and Torsten Ochsenreiter1

This study reveals the involvement of the translationally controlled tumor protein TCTP in cell cycle regulation and heat stress response in the bloodstream form of Trypanosoma brucei, shedding light on its role in these cellular processes.

Single telomere length analysis in Ustilago maydis, a high-resolution tool for examining fungal telomere length distribution and C-strand 5’-end processing

Ganduri Swapna1, Eun Young Yu1 and Neal F. Lue1, 2

This article introduces the development of single telomere length analysis (STELA) for Ustilago maydis, a basidiomycete fungus, enabling the precise measurement of telomere lengths and distributions. The study demonstrates STELA's utility in revealing the existence of relatively short telomeres in wild-type cells, preferential loss of long telomeres in a mutant defective in telomere replication, and the characterization of telomere C-strand 5’ ends, highlighting U. maydis as a strong model for telomere research.

Temporal analysis of the autophagic and apoptotic phenotypes in Leishmania parasites

Louise Basmaciyan1, Laurence Berry2, Julie Gros3, Nadine Azas3 and Magali Casanova3

This article details a comprehensive analysis of miltefosine-induced cell death and autophagy in Leishmania major, providing criteria for clear identification of apoptotic and autophagic cells, demonstrating the sequential nature of autophagy followed by apoptosis in nutrient-deprived conditions, and cautioning against using the generic kinase inhibitor staurosporine as a Leishmania apoptosis inducer, with the aim of improving the understanding of these processes and their targeting for new anti-leishmanial drugs.

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

Stephen D. Willis1, David C. Stieg1, Kai Li Ong2, Ravina Shah1,3, Alexandra K. Strich1,4, Julianne H. Grose2 and Katrina F. Cooper1

This article explores the response of eukaryotic cells to environmental stress, highlighting the role of the conserved cyclin C-Cdk8 kinase in determining pro-survival or pro-death programs. Specifically, it discusses how oxidative stress triggers the destruction of Med13 by the SCFGrr1 ubiquitin ligase, releasing cyclin C to promote mitochondrial fission and cell death in Saccharomyces cerevisiae. Additionally, it reveals that the AMP kinase Snf1 activates a separate degron in Med13, contributing to the complex regulation of Med13 degradation following H2O2 stress through the coordination of the cell wall integrity and MAPK pathways.

Importance of polyphosphate in the Leishmania life cycle

Kid Kohl1, Haroun Zangger1, Matteo Rossi1, Nathalie Isorce1, Lon-Fye Lye2, Katherine L. Owens2, Stephen M. Beverley2, Andreas Mayer1 and Nicolas Fasel1

This article explores the importance of polyphosphate (polyP) in Leishmania parasites, emphasizing the role of the polyP polymerase VTC4 and its impact on parasite survival at higher temperatures. Additionally, it discusses the effects of VTC4 knockout in mouse infections, noting a delay in lesion formation and strong pathology in L. major VTC4 knockout, without confirmation through complementation and no alteration in L. guyanensis infections in mice with VTC4 knockdown.

Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence

Maurizio D. Baroni1, Sonia Colombo2 and Enzo Martegani2

This article describes the effects of salicylate, the main metabolite of aspirin, on S. cerevisiae cells. It outlines how salicylate influences glucose transport, sugar phosphate biosynthesis, and apoptosis, particularly in MnSOD-deficient cells. Furthermore, it emphasizes the significant impact of salicylate on the exit from a quiescent state, inhibiting growth recovery and viability in long-term stationary phase cells. The passage also discusses the potential therapeutic implications of understanding the antagonistic relationship between cAMP and salicylate in targeting quiescent cancer cells with stem-like properties.

Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family

Anezia Kourkoulou1,#, Alexandros A. Pittis2,# and George Diallinas1

L-ascorbic acid (vitamin C) is an essential metabolite in animals and plants due to its role as an enzyme co-factor and antioxidant activity. Here, Kourkoulou et al. show further evidence that ascorbate-specific Nucleobase-Ascorbate Transporters (NATs) evolved by optimization of a sub-function of ancestral nucleobase transporters.

Valine biosynthesis in Saccharomyces cerevisiae is regulated by the mitochondrial branched-chain amino acid aminotransferase Bat1

Natthaporn Takpho1, Daisuke Watanabe1 and Hiroshi Takagi1

In Saccharomyces cerevisiae, the yeast, the Bat1 and Bat2 proteins, which are branched-chain amino acid aminotransferases, play distinct roles in valine biosynthesis and cell growth regulation, with Bat1 primarily located in the mitochondria and Bat2 in the cytosol, and the mitochondria being identified as the major site of valine biosynthesis in this yeast.

Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor

Damien J. Cabral1, Swathi Penumutchu1, Colby Norris1,2, Jose Ruben Morones-Ramirez3,4 and Peter Belenky1

Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. Here, Cabral et al. show that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.

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Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues

August 18, 2023

Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants

The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella

August 17, 2023

Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.

Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2

August 8, 2023

We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.

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

July 10, 2023

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

July 10, 2023

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

June 28, 2023

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

May 10, 2023

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

March 21, 2023

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

March 8, 2023

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.

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