Combined omics approaches reveal distinct responses between light and heavy rare earth elements in Saccharomyces cerevisiae

Grosjean, Nicolas; Jean, Marie Le; Armengaud, Jean; Schikora, Adam; Chalot, Michel; Gross, Elisabeth Maria; Blaudez, Damien

doi:10.1016/j.jhazmat.2021.127830

Cited by 11 publications

(12 citation statements)

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“…Several mutants responding to Ln exposure were knocked out for genes encoding proteins involved in the cell wall stress response and cell wall biosynthesis ( Figures 3 , 4 ; Supplementary Table S7 ). In a recent transcriptomics and proteomics analysis of S. cerevisiae , cell wall biosynthesis and organization-related pathways were upregulated in response to both La and Yb, supporting the strong implication of the cell wall as the first interface ( Grosjean et al, 2021 ). However, the mutants found in the present deletome analysis displayed distinct phenotypes under La or Yb exposure, supporting the need of complementary multi-scale approaches.…”

Section: Resultsmentioning

confidence: 86%

“…Transport and localization functions, which include vacuolar transport, endocytosis and vesicle-mediated transport, catabolic processes, and lipid metabolism, were highly represented among La- and Yb-responsive mutants ( Figure 3 ). Previously, endocytosis was also found as a primary pathway affected by these metals ( Pallares et al, 2021 ) together with lipids, amino acids, and carbohydrates metabolisms ( Grosjean et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…The chitin content of WT cells remained constant despite Ln exposure. Interestingly, upregulation of the chitin cell wall metabolic process and the 1,3-β-D-glucan biosynthesis pathways were observed by transcriptomics and proteomics ( Grosjean et al, 2021 ). This suggests that upregulation of these cell wall-related pathways is essential to maintain a proper cell wall structure, composition, and organization to compensate for Ln binding.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, by using an arrayed mutant collection screening, we demonstrated that some mutants that were previously found specific to HREEs, are also shared with La (e.g., ypl056c∆, ykr020w∆, ypl057c∆, ybr036c∆), expending the yeast core response to Ln, but also supporting the need for combining experimental approaches. In a recent paper, we combined transcriptomics and proteomics analyses on Saccharomyces cerevisiae exposed to La and Yb and most of the pathways impacted by Ln were found in each of these complementary approaches ( Grosjean et al, 2021 ). This multi-scale analysis (deletome, transcriptome, and proteome) of the response of yeast to Ln provides valuable target genes, proteins, and pathways involved in Ln toxicity response and detoxification that complements and expands on previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…A few studies have hypothesized that LREEs and HREEs may induce different responses, based on their relative reactivity and chemical differences ( Gonzalez et al, 2014 ). In addition to their different toxicity levels (HREEs > LREEs ( Tyler, 2004 ; Gonzalez et al, 2014 ; Goecke et al, 2017 )), only a few studies revealed the specific modes of action of these two REE groups with a single multi-scale analysis directly comparing the differential effect of two Ln ( Grosjean et al, 2021 ). As such, specific accumulation of LREEs has been reported in ferns ( Grosjean et al, 2020 ), while angiosperms preferentially translocate HREEs in their aboveground tissues ( Liu et al, 2018 ; Grosjean et al, 2019 ), thereby suggesting different transport systems between LREEs and HREEs.…”

Section: Introductionmentioning

confidence: 99%

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Genome-Wide Mutant Screening in Yeast Reveals that the Cell Wall is a First Shield to Discriminate Light From Heavy Lanthanides

et al. 2022

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The rapidly expanding utilization of lanthanides (Ln) for the development of new technologies, green energies, and agriculture has raised concerns regarding their impacts on the environment and human health. The absence of characterization of the underlying cellular and molecular mechanisms regarding their toxicity is a caveat in the apprehension of their environmental impacts. We performed genomic phenotyping and molecular physiology analyses of Saccharomyces cerevisiae mutants exposed to La and Yb to uncover genes and pathways affecting Ln resistance and toxicity. Ln responses strongly differed from well-known transition metal and from common responses mediated by oxidative compounds. Shared response pathways to La and Yb exposure were associated to lipid metabolism, ion homeostasis, vesicular trafficking, and endocytosis, which represents a putative way of entry for Ln. Cell wall organization and related signaling pathways allowed for the discrimination of light and heavy Ln. Mutants in cell wall integrity-related proteins (e.g., Kre1p, Kre6p) or in the activation of secretory pathway and cell wall proteins (e.g., Kex2p, Kex1p) were resistant to Yb but sensitive to La. Exposure of WT yeast to the serine protease inhibitor tosyl phenylalanyl chloromethyl ketone mimicked the phenotype of kex2∆ under Ln, strengthening these results. Our data also suggest that the relative proportions of chitin and phosphomannan could modulate the proportion of functional groups (phosphates and carboxylates) to which La and Yb could differentially bind. Moreover, we showed that kex2∆, kex1∆, kre1∆, and kre6∆ strains were all sensitive to light Ln (La to Eu), while being increasingly resistant to heavier Ln. Finally, shotgun proteomic analyses identified modulated proteins in kex2∆ exposed to Ln, among which several plasmalemma ion transporters that were less abundant and that could play a role in Yb uptake. By combining these different approaches, we unraveled that cell wall components not only act in Ln adsorption but are also active signal effectors allowing cells to differentiate light and heavy Ln. This work paves the way for future investigations to the better understanding of Ln toxicity in higher eukaryotes.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%