The essential gene <i>YMR134W</i> from <i>Saccharomyces cerevisiae</i> is important for appropriate mitochondrial iron utilization and the ergosterol biosynthetic pathway

Moretti-Almeida, Gabriel; Netto, L.E.S.; Monteiro, Gisele

doi:10.1016/j.febslet.2013.07.024

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…Defects in this step lead to the accumulation of toxic intermediates of the methyl sterol oxidase reaction that increase mitochondrial oxidation and affect the stability of the yeast frataxin homolog Ffh1, which is implicated in mitochondrial iron metabolism [13]. As a consequence, erg29 mutants exhibit defects in iron-sulfur cluster assembly and mitochondrial iron accumulation [13,115]. These results emphasize the multiple connections between iron metabolism and ergosterol biosynthesis.…”

Section: Regulation By Iron Bioavailabilitymentioning

confidence: 95%

“…In any case, under iron deprivation, the loss of Dap1 is rescued by ERG11 overexpression but not by increasing heme biosynthesis [111]. In addition to Dap1, mutants in other components of ergosterol biosynthesis, such as in the essential genes ERG25 and ERG29, also lead to growth defects in low iron and respiratory conditions, respectively, due to impaired ergosterol production [114,115]. A recent study has revealed that, similarly to Erg25, Erg29 participates in the methyl sterol oxidase step of ergosterol biosynthesis [13].…”

Section: Regulation By Iron Bioavailabilitymentioning

confidence: 99%

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Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Jordá

Puig

2020

Genes

314

287

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Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. Ergosterol biosynthesis is a complex and highly energy-consuming pathway that involves the participation of many enzymes. Deficiencies in sterol biosynthesis cause pleiotropic defects that limit cellular proliferation and adaptation to stress. Thereby, fungal ergosterol levels are tightly controlled by the bioavailability of particular metabolites (e.g., sterols, oxygen and iron) and environmental conditions. The regulation of ergosterol synthesis is achieved by overlapping mechanisms that include transcriptional expression, feedback inhibition of enzymes and changes in their subcellular localization. In the budding yeast Saccharomyces cerevisiae, the sterol regulatory element (SRE)-binding proteins Upc2 and Ecm22, the heme-binding protein Hap1 and the repressor factors Rox1 and Mot3 coordinate ergosterol biosynthesis (ERG) gene expression. Here, we summarize the sterol biosynthesis, transport and detoxification systems of S. cerevisiae, as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of ERG genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.

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Section: Regulation By Iron Bioavailabilitymentioning

confidence: 95%

Section: Regulation By Iron Bioavailabilitymentioning

confidence: 99%

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Jordá

Puig

2020

Genes

314

287

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“…The bm-8 mutant allele was a missense mutation in YMR134W, which encoded for a protein of unknown function. Moretti-Almeida et al (14) reported that a temperature-sensitive allele of YMR134W showed low mitochondrial iron accumulation at the restrictive temperature along with defects in ergosterol synthesis. Here, we report a detailed description of YMR134W, herein referred to as ERG29.…”

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confidence: 99%

Altered sterol metabolism in budding yeast affects mitochondrial iron–sulfur (Fe-S) cluster synthesis

Chen

Kaplan

et al. 2018

Journal of Biological Chemistry

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Ergosterol synthesis is essential for cellular growth and viability of the budding yeast , and intracellular sterol distribution and homeostasis are therefore highly regulated in this species. Erg25 is an iron-containing C4-methyl sterol oxidase that contributes to the conversion of 4,4-dimethylzymosterol to zymosterol, a precursor of ergosterol. The gene encodes an endoplasmic reticulum (ER)-associated protein, and here we identified a role for Erg29 in the methyl sterol oxidase step of ergosterol synthesis. deletion resulted in lethality in respiring cells, but respiration-incompetent (Rho or Rho) cells survived, suggesting that Erg29 loss leads to accumulation of oxidized sterol metabolites that affect cell viability. Down-regulation of expression in Δ cells indeed led to accumulation of methyl sterol metabolites, resulting in increased mitochondrial oxidants and a decreased ability of mitochondria to synthesize iron-sulfur (Fe-S) clusters due to reduced levels of Yfh1, the mammalian frataxin homolog, which is involved in mitochondrial iron metabolism. Using a high-copy genomic library, we identified suppressor genes that permitted growth of Δ cells on respiratory substrates, and these included genes encoding the mitochondrial proteins Yfh1, Mmt1, Mmt2, and Pet20, which reversed all phenotypes associated with loss of Of note, loss of Erg25 also resulted in accumulation of methyl sterol metabolites and also increased mitochondrial oxidants and degradation of Yfh1. We propose that accumulation of toxic intermediates of the methyl sterol oxidase reaction increases mitochondrial oxidants, which affect Yfh1 protein stability. These results indicate an interaction between sterols generated by ER proteins and mitochondrial iron metabolism.

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“…A role for CTH2 in increasing resistance to ROS when this gene is overexpressed has been proposed (Matsuo et al, 2017). In case of YMR134W (ERG29), its function is related to ergosterol biosynthesis and has been tied to iron metabolism too (Moretti-Almeida et al, 2013). The common upregulation of YER037W (PHM8), which is involved in lysophosphatidic acid hydrolysis in response to phosphate starvation, suggests low availability of this nutrient too (Vardi et al, 2014).…”

Section: Transcriptional Response Of S Cerevisiae Cells To Differentmentioning

confidence: 99%

Commonalities and Differences in the Transcriptional Response of the Model Fungus Saccharomyces cerevisiae to Different Commercial Graphene Oxide Materials

Laguna-Teno¹,

Suárez-Diez²,

Tamayo-Ramos³

2020

Front. Microbiol.

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Graphene oxide has become a very appealing nanomaterial during the last years for many different applications, but its possible impact in different biological systems remains unclear. Here, an assessment to understand the toxicity of different commercial graphene oxide nanomaterials on the unicellular fungal model organism Saccharomyces cerevisiae was performed. For this task, an RNA purification protocol was optimized to avoid the high nucleic acid absorption capacity of graphene oxide. The developed protocol is based on a sorbitol gradient separation process for the isolation of adequate ribonucleic acid levels (in concentration and purity) from yeast cultures exposed to the carbon derived nanomaterial. To pinpoint potential toxicity mechanisms and pathways, the transcriptome of S. cerevisiae exposed to 160 mg L −1 of monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) was studied and compared. Both graphene oxide products induced expression changes in a common group of genes (104), many of them related to iron homeostasis, starvation and stress response, amino acid metabolism and formate catabolism. Also, a high number of genes were only differentially expressed in either GO (236) or GOC (1077) exposures, indicating that different commercial products can induce specific changes in the physiological state of the fungus.

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The essential gene YMR134W from Saccharomyces cerevisiae is important for appropriate mitochondrial iron utilization and the ergosterol biosynthetic pathway

Cited by 7 publications

References 30 publications

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Altered sterol metabolism in budding yeast affects mitochondrial iron–sulfur (Fe-S) cluster synthesis

Commonalities and Differences in the Transcriptional Response of the Model Fungus Saccharomyces cerevisiae to Different Commercial Graphene Oxide Materials

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