Research, 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.
Deletion of AIF1 but not of YCA1/MCA1 protects Saccharomyces cerevisiae and Candida albicans cells from caspofungin-induced programmed cell death
Christopher Chin1,2,#, Faith Donaghey1,#, Katherine Helming1,3,#, Morgan McCarthy1,#, Stephen Rogers1, and Nicanor Austriaco1
This work suggests that deleting AIF1 but not YCA1/MCA1 protects S. cerevisiae and Candida albicans from caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death in Candida but also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.
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.
Early manifestations of replicative aging in the yeast Saccharomyces cerevisiae.
Maksim I. Sorokin1,3, Dmitry A. Knorre2,3, and Fedor F. Severin2,3
The data preseted herein suggest that retrograde signaling starts to malfunction in relatively young cells, leading to accumulation of heterogeneous mitochondria within one cell. The latter may further contribute to a decline in stress resistances.
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.
Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging
March 3, 2016
Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. The authors show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Their results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures.
Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity
February 19, 2016
Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.
Mitochondrial proteomics of the acetic acid – induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii – derived hybrid strain
January 22, 2016
Very high concentrations of acetic acid at low pH induce programmed cell death (PCD) in both the experimental model Saccharomyces cerevisiae and in Zygosaccharomyces bailii, the latter being considered the most problematic acidic food spoilage yeast due to its remarkable intrinsic resistance to this food preservative. This study offers insights into the mechanisms involved in acetic acid - induced PCD in the Z. bailii-derived hybrid strain ISA1307 by analyzing the yeast mitochondrial protein expression profile of cells challenged by acetic acid.
The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae
January 18, 2016
Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.
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.