The unfolded protein response of yeast &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; and other organisms

Tran, Duc Minh

doi:10.5685/plmorphol.30.15

Cited by 7 publications

(3 citation statements)

References 86 publications

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“…The UPR of A. fumigatus is a two-component relay that generally follows the canonical pathway described in Saccharomyces cerevisiae [10][11][12]. The sensing module, IreA, is an ER transmembrane protein whose luminal domain interacts with the protein chaperone BipA/ Kar2 under homeostatic conditions.…”

Section: Introductionmentioning

confidence: 99%

The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection

Kamath,

Lightfoot,

Adams

et al. 2023

PLoS Pathog

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The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates the mRNA of the transcription factor HacA. Spliced hacA accumulates under conditions of acute ER stress in vitro, and UPR null mutants are hypovirulent in a murine model of invasive pulmonary infection. In this report, we demonstrate that a hacA deletion mutant (ΔhacA) is furthermore avirulent in a model of fungal keratitis, a corneal infection, and an important cause of ocular morbidity and unilateral blindness worldwide. Interestingly, we demonstrate that A. fumigatus hacA is spliced in infected lung samples, but not in the cornea, suggesting the amount of ER stress experienced by the fungus varies upon the host niche. To better understand how the UPR contributes to fungal cell biology across a spectrum of ER-stress levels, we employed transcriptomics on the wild-type and ΔhacA strains in glucose minimal media (low stress), glucose minimal media with dithiothreitol (high stress), and gelatin minimal media as a proxy for the nutrient stress encountered in the cornea (mid-level stress). These data altogether reveal a unique HacA-dependent transcriptome under each condition, suggesting that HacA activity is finely-tuned and required for proper fungal adaptation in each environment. Taken together, our results indicate that the fungal UPR could serve as an important antifungal target in the setting of both invasive pulmonary and corneal infections.

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Section: Introductionmentioning

confidence: 99%

The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection

Kamath,

Lightfoot,

Adams

et al. 2023

PLoS Pathog

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“…Also in animal and plant cells, Ire1 is involved in the splicing of mRNAs encoding transcription factors, namely XBP1 in metazoans and bZIP60 in plants ( Tran and Kimata, 2018 ). On the other hand, Ire1 promotes the degradation of mRNAs that mainly encode ER client proteins in these species ( Coelho and Domingos, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in Pichia pastoris cells independent of HAC1

Fauzee

Yoshida

2023

Front. Microbiol.

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In eukaryotic species, dysfunction of the endoplasmic reticulum (ER), namely, ER stress, provokes a cytoprotective transcription program called the unfolded protein response (UPR). The UPR is triggered by transmembrane ER-stress sensors, including Ire1, which acts as an endoribonuclease to splice and mature the mRNA encoding the transcription factor Hac1 in many fungal species. Through analyses of the methylotrophic yeast Pichia pastoris (syn. Komagataella phaffii), we revealed a previously unknown function of Ire1. In P. pastoris cells, the IRE1 knockout mutation (ire1Δ) and HAC1 knockout mutation (hac1Δ) caused only partially overlapping gene expression changes. Protein aggregation and the heat shock response (HSR) were induced in ire1Δ cells but not in hac1Δ cells even under non-stress conditions. Moreover, Ire1 was further activated upon high-temperature culturing and conferred heat stress resistance to P. pastoris cells. Our findings cumulatively demonstrate an intriguing case in which the UPR machinery controls cytosolic protein folding status and the HSR, which is known to be activated upon the accumulation of unfolded proteins in the cytosol and/or nuclei.

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“…This cellular protective response is called the unfolded protein response (UPR), and is mediated, at least in part, by the ER-located transmembrane protein Ire1, which works as an endoribonuclease [3]. In the budding yeast Saccharomyces cerevisiae, Ire1 is activated strictly in an ER stress-dependent manner, and facilitates the splicing of HAC1 mRNA, which is then translated into a transcription-factor protein that is responsible for the UPR [4].…”

Section: Introductionmentioning

confidence: 99%

Aeration mitigates endoplasmic reticulum stress in Saccharomyces cerevisiae even without mitochondrial respiration

Phuong¹,

Ishiwata-Kimata²,

Nishi³

et al. 2021

Microb Cell

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Saccharomyces cerevisiae is a facultative anaerobic organism that grows well under both aerobic and hypoxic conditions in media containing abundant fermentable nutrients such as glucose. In order to deeply understand the physiological dependence of S. cerevisiae on aeration, we checked endoplasmic reticulum (ER)-stress status by monitoring the splicing of HAC1 mRNA, which is promoted by the ER stress-sensor protein, Ire1. HAC1-mRNA splicing that was caused by conventional ER-stressing agents, including low concentrations of dithiothreitol (DTT), was more potent in hypoxic cultures than in aerated cultures. Moreover, growth retardation was observed by adding low-dose DTT into hypoxic cultures of ire1∆ cells. Unexpectedly, aeration mitigated ER stress and DTT-induced impairment of ER oxidative protein folding even when mitochondrial respiration was halted by the ro mutation. An ER-located protein Ero1 is known to directly consume molecular oxygen to initiate the ER protein oxidation cascade, which promotes oxidative protein folding of ER client proteins. Our further study using ero1-mutant strains suggested that, in addition to mitochondrial respiration, this Ero1-medaited reaction contributes to mitigation of ER stress by molecular oxygen. Taken together, here we demonstrate a scenario in which aeration acts beneficially on S. cerevisiae cells even under fermentative conditions.

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The unfolded protein response of yeast <i>Saccharomyces cerevisiae</i> and other organisms

Cited by 7 publications

References 86 publications

The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection

The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection

Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in Pichia pastoris cells independent of HAC1

Aeration mitigates endoplasmic reticulum stress in Saccharomyces cerevisiae even without mitochondrial respiration

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