Research, Research Articles
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.
Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling
Viktor Scheidt1,#, André Jüdes1,#, Christian Bär1,2,#, Roland Klassen1 and Raffael Schaffrath1
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.
Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei
Neta Shlezinger1,#, Elad Eizner1,2,#, Stas Dubinchik2, Anna Minz-Dub1, Rachel Tetroashvili1, Adi Reider1, Amir Sharon1
This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.
Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan
Ivan Orlandi1,2, Damiano Pellegrino Coppola2 and Marina Vai1,2
This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.
Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin
October 24, 2014
This study reports the identification of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) and shows that specific ARBs increase yeast tolerance to Cu and Cp, and affect markers of Cu-induced apoptosis. Likewise, this study finds that specific ARBs increase human cell line tolerance to Cu and decrease the prevalence of apoptotic markers.
An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids
October 1, 2014
This work describes a novel family of type I membrane proteins ("invariant glycoproteins") and proposes them as trypanosomatid-specific ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, that utilise oligomerisation as an ER retention mechanism.
Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program
September 1, 2014
Using multiple approaches, this work implies a nucleosome focusing event as a key step that resets transcription during the respiratory oscillation.
Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae
August 27, 2014
This work characterizes the involvement of MAPK signaling pathways in cell death induced by acetic acid in Saccharomyces cerevisiae.
Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa
August 9, 2014
The results presented here reveal that in Neurospora crassa, extracellular Ca2+ modulates cell death and the transcriptional alterations induced by staurosporine, and lead to the identification of two novel putative Ca2+-binding proteins, encoded by the NCU08524 and NCU06607 genes.
Multiple metabolic requirements for size homeostasis and initiation of division in Saccharomyces cerevisiae
August 1, 2014
This article reveals an unexpected diversity in the G1 cell cycle phenotypes of metabolic and biosynthetic Saccharomyces cerevisiae mutants, suggesting that growth requirements for cell division are multiple, distinct and imposed throughout the G1 phase of the cell cycle.
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.
Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina
June 22, 2014
In this article, paraquat is used to experimentally induce strong cellular oxidative stress in Podospora anserina wild-type cultures of different age, finding that this treatment has profound effects on gene expression, growth and lifespan.
Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles against Scedosporium prolificans via induction of apoptosis
June 2, 2014
This article reports for the first time that posaconazole (PCZ) or itraconazolein (ICZ) in combination with the calcineurin inhibitor tacrolimus or the Hsp90 inhibitor 17-demethoxy-17-(2-propenylamino) geldanamycin renders S. prolificans exquisitely sensitive to PCZ or ICZ via apoptosis.
At neutral pH the chronological lifespan of Hansenula polymorpha increases upon enhancing the carbon source concentrations
May 20, 2014
The data presented in this work indicate that in H. polymorpha at neutral pH the chronological lifespan invariably extends upon increasing the carbon source concentration.