Research, Research Articles

A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis

Kanako Hagihara1, Kanako Kinoshita1, Kouki Ishida1, Shihomi Hojo1, Yoshinori Kameoka1, Ryosuke Satoh1, Teruaki Takasaki1 and Reiko Sugiura1

Fingolimod hydrochloride (FTY720) is an immune modulator for multiple sclerosis that also induces cancer cell apoptosis through reactive oxygen species generation, with a new study using fission yeast uncovering a gene network related to ROS homeostasis as a possible mechanism of FTY720's toxicity.

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto1, Stephen P. Dearth2, Eric D. Tague2, Shawn R. Campagna2 and Diana M. Downs1

In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell.

The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development

Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3

In this study the authors demonstrate that, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development against the malaria parasite Plasmodium falciparum.

Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6’)-Im

Clyde A. Smith1, Monolekha Bhattacharya2, Marta Toth2, Nichole K. Stewart2 and Sergei B. Vakulenko2

AAC(6')-Im, a monofunctional acetyltransferase, imparts increased resistance to certain aminoglycosides compared to its bifunctional homolog AAC(6')-Ie, with structural studies revealing differences in substrate binding that explain the discrepancies in their enzymatic activity and resistance profiles.

Cross-species complementation of bacterial- and eukaryotic-type cardiolipin synthases

Petra Gottier1, Mauro Serricchio1, Rita Vitale2, Angela Corcelli2, and Peter Bütikofer1

This article shows that cardiolipin is crucial for cellular respiration and membrane integrity, with cardiolipin synthase enzymes like TbCLS in Trypanosoma brucei being potential drug targets due to their essential role in survival. The study demonstrates TbCLS's ability to restore cardiolipin production in yeast, highlighting the specificity and potential co-localization required for cardiolipin synthesis and remodeling, and underscoring the differences between eukaryotic and prokaryotic cardiolipin synthase mechanisms.

Identification of SUMO conjugation sites in the budding yeast proteome

Miguel Esteras1, I-Chun Liu1, Ambrosius P. Snijders2, Adam Jarmuz1 and Luis Aragon1

The authors present a proteomic study that mapped SUMO acceptor lysines in budding yeast, identifying 257 potential conjugation sites, including both known and novel substrates, and providing a significant resource for future research into the functional implications of SUMOylation in yeast.

Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

Jinglin L. Xie2,#, Iryna Bohovych3,#, Erin O.Y. Wong2, Jean-Philippe Lambert4, Anne-Claude Gingras2,4, Oleh Khalimonchuk3,5,6, Leah E. Cowen2 and Michelle D. Leach1,2

The authors descibe the role of the Hsp40 chaperone Ydj1 in Candida albicans, noting its localization to the cytosol and mitochondrial membrane, its necessity for stress responses and filamentation, and its involvement in a protein interaction network related to co-chaperones, filamentation regulators, and mitochondrial processing peptidases, with a particular focus on the impact of Ydj1 on mitochondrial morphology, function, and the import of precursor proteins.

Farnesol inhibits translation to limit growth and filamentation in C. albicans and S. cerevisiae

Nkechi E. Egbe1,2, Tawni O. Dornelles1, Caroline M. Paget1, Lydia M. Castelli1,3 and Mark P. Ashe1

Farnesol, a quorum-sensing molecule, inhibits the switch from yeast to filamentous growth in Candida albicans by impeding translation initiation, differing from fusel alcohols that affect the initiation factor eIF2B, as it disrupts mRNA interaction with the ribosome and prevents preinitiation complex formation.

Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10

Katharina Eydt1,2, Karen M. Davies3, Christina Behrendt4, Ilka Wittig1,5 and Andreas S. Reichert1,2,4,*

This article investigates the roles of MICOS subunits Mic27 and Mic10, revealing their antagonistic and cooperative interactions in crista junction formation and cristae membrane curvature, and proposes a model where F1FO-ATP synthase is connected to MICOS, influencing CJ formation.

Previous Next

Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion

October 31, 2014

This article investigates the role of Yap1 during the production of recombinant secretory proteins in glucose based growth conditions in Pichia pastoris, and reports a novel role of Yap1 during ER-resident oxidative protein folding.

Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

October 29, 2014

This study confirms the importance of specific genes in growth and fermentation activity of Saccharomyces cerevisiae at low temperature.

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.

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.

Previous Next