Research, Research Articles

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

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

Erika Cruz-Bonilla1, Sergio E. Campos2, Soledad Funes3, Cei Abreu-Goodger4 and Alexander DeLuna1,2,*

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 <i>Podospora anserina</i> development

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

Melisa Álvarez-Sánchez1, Matías Ramírez-Noguez1, Beatriz Aguirre-López1 and Leonardo Peraza-Reyes1

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 <i>sit1</i> gene in normal germination of spores and virulence of the <i>Mucor lusitanicus</i>

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

Bernadett Vágó1,2, Kitti Bauer1,2, Naomi Varghese1,2, Sándor Kiss-Vetráb1,2, Sándor Kocsubé1,2, Mónika Varga1,2, András Szekeres1,2, Csaba Vágvölgyi1,2, Tamás Papp1,2,3,# and Gábor Nagy1,2,3,#

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

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

Fei Zhao1,#, Lei Wang2,3,4,#, Dongjie Du5, Heaven Zhao6,7, Geng Tian6,7, Yufeng Li2,3,8, Yankun Liu2,8,9, Zhiwu Wang2,3,10, Dasheng Liu11, Jingwu Li2,3,12, Lei Ji6,7 and Hong Zhao1

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 <i>Escherichia coli</i> in response to ciprofloxacin, revealing high-persistence strains

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

Valeria Pérez-Villalobos1, Roberto Vidal2, Marcela A. Hermoso3,4 and Paula Bustamante1

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 <i>Trypanosoma cruzi</i>

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

Janaína de Freitas Nascimento1, María Julia Barisón1, Gabriela Torres Montanaro1, Letícia Marchese1, Rodolpho Ornitz Oliveira Souza1, Letícia Sophia Silva2, Alessandra Aparecida Guarnieri2 and Ariel Mariano Silber1

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

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

John-Patrick Alao1, Juhi Kumar1, Despina Stamataki2 and Charalampos Rallis1

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 <i>Saccharomyces cerevisiae</i> by modulating arginine biosynthesis

Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

Nicolás Urtasun1,2,a, Sebastián Aníbal Muñoz1,a, Martín Arán3 and Mariana Bermúdez-Moretti1

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.

An adenine model of inborn metabolism errors alters TDP-43 aggregation and reduces its toxicity in yeast revealing insights into protein misfolding diseases

An adenine model of inborn metabolism errors alters TDP-43 aggregation and reduces its toxicity in yeast revealing insights into protein misfolding diseases

Sangeun Park, Sei-Kyoung Park, Peter Blair and Susan W. Liebman

This work offers new insights into the potential interactions between me-tabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.

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A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels

November 12, 2018

In this study, a humanized yeast system for functional studies on higher eukaryotic Phosphatidylinositol 3-kinase (PI3K) was developed by restricting PI3K activity in yeast to specific plasma membrane microdomains, utilizing engineered reporters to monitor activity at a single-cell level and employing novel tools to study the performance of yeast plasma membrane (PM) microdomain-directed PI3K, revealing location-specific effects on yeast growth and endocytosis.

A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans

October 31, 2018

This study demonstrates that the bipolar disorder drug lithium inhibits the formation of key virulence factors, biofilm, and polysaccharide capsule, in Cryptococcus neoformans by dysregulating the ubiquitin/proteasome system, shedding light on the impact of lithium and providing insights into potential alternative pharmaceutical approaches for combating this fungal pathogen.

Nutritional and meiotic induction of transiently heritable stress resistant states in budding yeast

October 29, 2018

This study demonstrates that transient exposures to environmental stresses induce persistent states of elevated stress resistance in yeast cells, termed cellular memory, suggesting a form of epigenetic inheritance, and shows that this phenomenon occurs not only in meiotically produced spores but also in haploid cells subjected to glucose withdrawal, adding new insights into the developmentally and nutritionally induced cellular memory.

Specific mutations in the permease domain of septal protein SepJ differentially affect functions related to multicellularity in the filamentous cyanobacterium Anabaena

October 16, 2018

In this study, the multifunctional roles of the SepJ protein in the multicellular function of the Anabaena filament were investigated, revealing that specific amino acids and stretches within the protein are essential for the formation of long filaments, heterocyst differentiation, and intercellular communication, shedding light on the structure and diverse functions of SepJ in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.

Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae

October 1, 2018

This study examined the capability of trehalose-6-phosphate synthase (TPS1) homologues from various species to complement the phenotypic defects of a Saccharomyces cerevisiae tps1 mutant, resulting in the classification of complementation into different groups based on metabolic patterns and fermentation capacity, shedding light on the role of TPS1 and trehalose-6-phosphate (T6P) as critical factors in sugar fermentation and glucose repression.

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

August 7, 2018

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

August 1, 2018

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

June 25, 2018

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

June 22, 2018

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

March 26, 2018

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.

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