Mitochondrial Ferredoxin Determines Vulnerability of Cells to Copper Excess.

The essential micronutrient copper is tightly regulated in organisms, as environmental exposure or homeostasis defects can cause toxicity and neurodegenerative disease. The principal target(s) of copper toxicity have not been pinpointed, but one key effect is impaired supply of iron-sulfur (FeS) clusters to the essential protein Rli1 (ABCE1). Here, to find upstream FeS biosynthesis/delivery protein(s) responsible for this, we compared copper sensitivity of yeast-overexpressing candidate targets.

Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.

There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy.

Phenotypic heterogeneity is a selected trait in natural yeast populations subject to environmental stress.

Populations of genetically uniform microorganisms exhibit phenotypic heterogeneity, where individual cells have varying phenotypes. Such phenotypes include fitness-determining traits. Phenotypic heterogeneity has been linked to increased population-level fitness in laboratory studies, but its adaptive significance for wild microorganisms in the natural environment is unknown.

The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species.

Oxidative stress mediated by reactive oxygen species (ROS) is linked to degenerative conditions in humans and damage to an array of cellular components. However, it is unclear which molecular target(s) may be the primary "Achilles' heel" of organisms, accounting for the inhibitory action of ROS. Rli1p (ABCE1) is an essential and highly conserved protein of eukaryotes and archaea that requires notoriously ROS-labile cofactors (Fe-S clusters) for its functions in protein synthesis.

Heterogeneous expression of the virulence-related adhesin Epa1 between individual cells and strains of the pathogen Candida glabrata.

We investigated the relevance of gene expression heterogeneity to virulence properties of a major fungal pathogen, Candida glabrata. The organism's key virulence-associated factors include glycosylphosphatidylinositol-anchored adhesins, encoded subtelomerically by the EPA gene family. Individual-cell analyses of expression revealed very striking heterogeneity for Epa1, an adhesin that mediates ∼95% of adherence to epithelial cells in vitro.

Candida argentea sp. nov., a copper and silver resistant yeast species.

A new yeast species was isolated from the sediment under metal-contaminated effluent from a disused metal mine in mid-Wales, UK. BLAST searching with DNA sequence amplified from the ribosomal 26S D1/D2 and ITS regions did not reveal a close match with any previously described species (≥6 % and 3 % divergence, respectively). Phylogenetic analysis indicated that the species was a member of the Saccharomycetales, but did not group closely with other established species, the nearest relative being Wickerhamia fluorescens although bootstrap support was not strong.

Chromate toxicity and the role of sulfur.

The molecular mode(s)-of-action of the toxic metal chromium has yet to be fully resolved. This Mini review focuses on interactions between chromate and sulfur in biological systems. Cr binds sulfur ligands, with cysteine and glutathione having the capacity to aggravate or ameliorate Cr toxicity.

Chromate-induced sulfur starvation and mRNA mistranslation in yeast are linked in a common mechanism of Cr toxicity.

Toxicity of the environmental carcinogen chromate is known to involve sulfur starvation and also error-prone mRNA translation. Here we reconcile those facts using the yeast model. We demonstrate that: (i) cysteine and methionine starvation mimic Cr-induced translation errors, (ii) genetic suppression of S starvation suppresses Cr-induced mistranslation, and (iii) mistranslation requires cysteine and methionine biosynthesis.

Actin-mediated endocytosis limits intracellular Cr accumulation and Cr toxicity during chromate stress.

Chromate toxicity is well documented, but the underlying toxic mechanism(s) has yet to be fully elucidated. Following a Cr toxicity screen against > 6000 heterozygous yeast mutants, here we show that Cr resistance requires normal function of the cortical actin cytoskeleton. Furthermore, Cr-stressed yeast cells exhibited an increased number of actin patches, the sites of endocytosis.