Research, Research Articles
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.
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.
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.
Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection
December 3, 2019
This study reveals that the plasma membrane SNARE proteins SNAP-23 and Syntaxin 4 are crucial for Chlamydia trachomatis development by regulating lipid droplet homeostasis and supporting the formation of infectious progeny within host cells.
Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane
November 19, 2019
Secretins, essential components of bacterial secretion systems, can be expressed in yeast and show differential dependencies on mitochondrial import and assembly factors for membrane integration, suggesting diverse pathways for their assembly into the bacterial outer membrane.
Metabolic reprogramming of Salmonella infected macrophages and its modulation by iron availability and the mTOR pathway
November 14, 2019
This article shows that iron plays a critical role in both the immune response and metabolic reprogramming of macrophages during infection, influencing the TCA cycle and mTOR pathway, with implications for the growth of intracellular bacteria like Salmonella.
Transcriptomic and chemogenomic analyses unveil the essential role of Com2-regulon in response and tolerance of Saccharomyces cerevisiae to stress induced by sulfur dioxide
September 30, 2019
This article shows that in the presence of sulfur dioxide (SO2), the transcription factor Com2 plays a critical role in the tolerance and response of Saccharomyces cerevisiae, affecting the expression of a majority of SO2-activated genes and contributing to the protection against stress induced by SO2 at an enologically relevant pH.
Network dynamics of the yeast methyltransferome
July 9, 2019
This article presents a systematic genetic analysis of methyltransferases (MTases) under normal and stress conditions, uncovering the complex and adaptive nature of the methyltransferome and discovering a potential connection between phospholipid methylation and histone methylation, suggesting interplay between lipid homeostasis and epigenetic regulation.
Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase
May 20, 2019
This article shows that the carbon source affects the abundance of ribonucleotide reductase (RNR) subunits in yeast, with a novel Mec1 signaling axis regulating Rnr3 independently of known DNA damage response pathways, and reveals Rnr3's unexpected role in mitochondrial function.