Research, Research Articles
In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor
Anne Silvestre1, 2, 3, 4, Aurélie Plaze1, 2, Patricia Berthon3, 4, Roman Thibeaux1, 2, Nancy Guillen1, 2 and Elisabeth Labruyère1, 2
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
Natalie K. Jones1,2,4,#, Nagla T.T. Arab1,3,#, Rawan Eid1,3,#, Nada Gharib1,5, Sara Sheibani1,2,6, Hojatollah Vali2, Chamel Khoury1, Alistair Murray1,2, Eric Boucher2, Craig A. Mandato2, Paul G. Young3 and Michael T. Greenwood1
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
R. Roshini Beenukumar1,#, Daniela Gödderz1,2,#, R. Palanimurugan1,3, and R. Jürgen Dohmen1
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
Kristin Graumann1,3,#, Frieder Schaumburg1,4,#, Thomas F. Reubold2, Diana Hippe1, Susanne Eschenburg2 and Carsten G. K. Lüder1
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...
Exogenous folates stimulate growth and budding of Candida glabrata
Afsaneh Porzoor and Ian G. Macreadie
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.
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites
Carine F. Djuika1, Jaime Huerta-Cepas2, Jude M. Przyborski3, Sophia Deil1, Cecilia P. Sanchez1, Tobias Doerks2, Peer Bork2, Michael Lanzer1 and Marcel Deponte1
Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
Chen Sun#, Jian Li#, Yu Cao, Gongbo Long and Bing Zhou
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release
March 15, 2019
This study investigated the role of Mitochondria-Associated Membranes (MAMs) in the regulation of apoptosis by analyzing the localization and function of the pro-apoptotic protein Bax in yeast, finding that disruption of MAMs by deletion of the MDM34 gene affects Bax's mitochondrial localization and the release of cytochrome c.
Chlamydia pneumoniae is present in the dental plaque of periodontitis patients and stimulates an inflammatory response in gingival epithelial cells
March 11, 2019
This study found that Chlamydia pneumoniae is present more frequently in the dental plaque of individuals with periodontal disease, can invade human gingival epithelial cells causing inflammatory responses, and may therefore be a contributing factor to periodontal disease and a potential indicator of risk.
Genome-wide analysis of yeast expression data based on a priori generated co-regulation cliques
January 22, 2019
The study demonstrates the use of predefined genome-wide expression cliques, derived from extensive microarray data, to effectively analyze and visualize the complete gene expression response across various cellular conditions in yeast.
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.