Research Articles
Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina
Matthias Wiemer and Heinz D. Osiewacz
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
Fazal Shirazi and Dimitrios P. Kontoyiannis
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
Adam Kawałek and Ida J. van der Klei
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.
Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA
Qiuqiang Gao1, Liang-Chun Liou2, Qun Ren2, Xiaoming Bao3 and Zhaojie Zhang2
In this work, the authors report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ0) and that this damage is related to elevated levels of SCW11 and salt stress-induced reactive oxygen species.
Protein oxidation in the intermembrane space of mitochondria is substrate-specific rather than general
Valentina Peleh1, Jan Riemer2, Andrew Dancis3 and Johannes M. Herrmann1
In this work, the authors suggest that in Saccharomyces cerevisiae, the Mia40-dependent oxidation of proteins in the intermembrane space only takes place in specific proteins and presumably relies on the presence of Mia40-binding sites.
Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells
Vitor Teixeira1,2, Tânia C. Medeiros1, Rita Vilaça1,2, Pedro Moradas-Ferreira1,2, and Vítor Costa1,2
Overall, this article shows that the TORC1-Sch9p axis is deregulated in Isc1p-deficient Saccharomyces cerevisiae cells, contributing to mitochondrial dysfunction, enhanced oxidative stress sensitivity and premature aging of isc1Δ cells.
Tracking autophagy during proliferation and differentiation of Trypanosoma brucei
William R. Proto1, Nathaniel G. Jones1, Graham H. Coombs2, and Jeremy C. Mottram1
This article provides insights into the function of autophagy, a cellular degradation and recycling pathway, in the protozoan parasite Trypanosoma brucei.
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...
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...
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
April 6, 2015
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
January 4, 2015
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...