Research, Research Articles
Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity
Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones
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
Joana F Guerreiro1, Belém Sampaio-Marques2,3, Renata Soares4, Ana Varela Coelho4, Cecília Leão2,3, Paula Ludovico2,3, Isabel Sá-Correia1
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
Ryo Higuchi-Sanabria1, Jason D. Vevea1,3, Joseph K. Charalel1,4, Maria L. Sapar5, Liza A. Pon1,2
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
Sei-Kyoung Park1, Kiira Ratia2, Mariam Ba1, Maria Valencik1 and Susan W. Liebman1,3
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
Patrick C. Thiaville1,2,3,4, Rachel Legendre4, Diego Rojas-Benítez5, Agnès Baudin-Baillieu4, Isabelle Hatin4, Guilhem Chalancon6, Alvaro Glavic5, Olivier Namy4, Valérie de Crécy-Lagard1,3
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
Figarella K1, Marsiccobetre S1, Arocha I1, Colina W2, Hasegawa M2,†, Rodriguez M2, Rodriguez-Acosta A3, Duszenko M4, Benaim G5, Uzcategui NL3
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
Donna Garvey Brickner, Robert Coukos and Jason H. Brickner
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
Michael E. Bond1, Rachel Brown1, Charalampos Rallis3,4, Jürg Bähler3,4 and Sara E. Mole1,2,3
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.
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.