Research Articles
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.
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.
Microbiota and metabolome dynamics induced by Shiga toxin-producing E. coli in an in vitro model of an infant’s colon
Mariana Izquierdo1,a, Deborah O’Sullivan2,a, Ophélie Uriot2, Morgane Brun2, Claude Durif2, Sylvain Denis2, Pablo Gallardo1, Cormac G M Gahan3-5, Lucie Etienne-Mesmin2, Stéphanie Blanquet-Diot2,b and Mauricio J. Farfan1.b
This study provides new evidence of the impact of EHEC in the microbiota and metabolome dynamics in an in vitro gut model that could be useful in understanding their physiopathology in this at-risk population, considering inter-individual variabilities in gut microbiota.
Ampicillin treatment in persister cell studies may cause non-physiological artifacts
Michel Fasnacht1,2, Hena Comic1,2, Isabella Moll1,2
This study shows at the example of L2 how insufficient purification of ampicillin persister cells can lead to the generation of non-physiological artifacts and provides a novel tool to improve the removal of residual cell debris.
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.
The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei
July 30, 2015
Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers...
In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor
July 6, 2015
Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1) stained the E. histolytica trophozoite...
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.
Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome
May 20, 2015
Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the...
Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly
May 4, 2015
Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that...