Research, Research Articles
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
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
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.
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.
Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs
January 18, 2016
The formation of small Aβ42 oligomers has been implicated as a toxic species in Alzheimer disease (AD). Here, we show that the mechanism of the PICALM, human AD risk factor, is likely to reduce the level of Aβ42 oligomers in cells. We screened FDA-approved drugs to identify candidates that prevent the formation of Aβ42 small oligomers using the yeast Aβ42-RF reporter system. We also showed that each of the drug hits counteract yeast and mammalian cell toxicity associated with Aβ42 small aggregates.
Global translational impacts of the loss of the tRNA modification t6A in yeast
December 18, 2015
The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. Analysis of codon occupancy rates suggests that one of the major roles of t6A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I34:C3 pairs while increasing the elongation rate of rare tRNAs and G34:U3 pairs. This work reveals that the consequences of t6A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.
Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes
December 11, 2015
The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
November 13, 2015
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
November 11, 2015
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
October 22, 2015
Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
September 21, 2015
In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.
The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway
September 6, 2015
Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway.
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
September 6, 2015
Varshavsky and colleagues solve a long-standing mystery in proteolysis! In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N‑terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in...
A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria
August 2, 2015
This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.