Research, Research Reports

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

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

Angela Cirigliano1,a, Antonia Amelina2,a, Elena Passarini2, Alessandra Ricelli1, Nicole Balasco1, Mattia Mori3, Bruno Botta4, Maria Egle De Stefano2,5, Claudio Papotto6, Claudia Guerriero2, Ada Maria Tata2,5 and Teresa Rinaldi2,*

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

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 Podospora anserina development

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

Eucaryotic cell functioning and development depend on the concerted activity of its organelles. In the model fungus Podospora anserina, sexual development involves a dynamic regulation of mitochondria, peroxisomes and the endoplasmic reticulum (ER), suggesting that their activity during this process is coordinated.

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

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 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 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

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 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.

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Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1

April 25, 2016

Candida albicans proliferates in two distinct cell types: blastopores and filaments. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We provide evidence that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Our genetic data suggest that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.

Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity

February 19, 2016

Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.

The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae

January 18, 2016

Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.

Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin

October 23, 2015

Shirazi et al. studied the effects of the cell wall inhibitor micafungin (MICA) on apoptosis in both MICA-susceptible (MICA-S) and MICA–non-susceptible (MICA-NS) Candida parapsilosis.

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

June 25, 2015

The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. This article reports that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. In sum, the results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.

Exogenous folates stimulate growth and budding of Candida glabrata

May 1, 2015

Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.

Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling

November 29, 2014

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.

Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae

July 6, 2014

The herein presented results indicate that in Saccharomyces cerevisiae, histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, it suggests that histidine cytotoxicity is involved in deficiency of mitochondrial copper.

Deletion of AIF1 but not of YCA1/MCA1 protects Saccharomyces cerevisiae and Candida albicans cells from caspofungin-induced programmed cell death

January 15, 2014

This work suggests that deleting AIF1 but not YCA1/MCA1 protects S. cerevisiae and Candida albicans from caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death in Candida but also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.

Early manifestations of replicative aging in the yeast Saccharomyces cerevisiae.

January 4, 2014

The data preseted herein suggest that retrograde signaling starts to malfunction in relatively young cells, leading to accumulation of heterogeneous mitochondria within one cell. The latter may further contribute to a decline in stress resistances.