Global Deletome Profile of Saccharomyces cerevisiae Exposed to the Technology-Critical Element Yttrium

Abstract

The emergence of the technology-critical-element yttrium as a contaminant in the environment raises concern regarding its toxicological impact on living organisms. The molecular mechanisms underlying yttrium toxicity must be delineated. We considered the genomic phenotyping of a mutant collection of Saccharomyces cerevisiae to be of particular interest to decipher key cellular pathways involved either in yttrium toxicity or detoxification mechanisms. Among the 4733 mutants exposed to yttrium, 333 exhibited modified growth, of which 56 were sensitive and 277 were resistant. Several functions involved in yttrium toxicity mitigation emerged, primarily vacuolar acidification and retrograde transport. Conversely, functional categories overrepresented in the yttrium toxicity response included cytoskeleton organization and endocytosis, protein transport and vesicle trafficking, lipid metabolism, as well as signaling pathways. Comparison with similar studies carried out using other metals and stressors showed a response pattern similar to nickel stress. One third of the identified mutants highlighted peculiar cellular effects triggered by yttrium, specifically those affecting the pheromone-dependent signaling pathway or sphingolipid metabolic processes. Taken together, these data emphasize the role of the plasma membrane as a hotspot for yttrium toxicity. The up-to-now lack of data concerning yttrium toxicity at the cellular and molecular levels makes this pioneer study using the model S. cerevisiae an excellent first basis for the assessment of yttrium toxicity toward eukaryotes.

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

“…For instance, plants that accumulate REEs display specific enrichment of either LREEs or HREEs (Grosjean et al, 2020(Grosjean et al, , 2019. Taken together, these few available studies support the need to elucidate the cellular and molecular mechanisms involved in the response to REEs, similar to work performed on the specific REE yttrium (Grosjean et al, 2018).…”

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

“…This lower number of mutants certainly arose from the fact that low concentrations (EC20) of La and Yb were used suggesting that more toxic concentrations is more appropriate to reveal the entire set of genes involved in the tolerance to Ln. The sublethal/lethal concentrations used here reproduce conditions usually applied for metal toxicogenomics in yeast, resulting in a similar number of sensitive ( Ruotolo et al, 2008 ) and resistant ( Ruotolo et al, 2008 ; Grosjean et al, 2018 ) mutants.…”

“…Clustering (heatmaps) was performed using the R package pheatmap. Ln-responsive mutants found in this study were compared with those from other studies carried out on Saccharomyces cerevisiae deletion mutant collections on Y ( Grosjean et al, 2018 ), Cd ( Jin et al, 2008 ; Ruotolo et al, 2008 ; Serero et al, 2008 ; Thorsen et al, 2009 ), Ni ( Ruotolo et al, 2008 ; Arita et al, 2009 ; Bleackley et al, 2011 ), Zn ( Pagani et al, 2007 ; Wang et al, 2007 ; Jin et al, 2008 ; Bleackley et al, 2011 ), Al ( Kakimoto et al, 2005 ; Tun et al, 2014 ), As ( Haugen et al, 2004 ; Thorsen et al, 2006 , 2009 ; Jin et al, 2008 ; Johnson et al, 2016a ), Cu ( Wang et al, 2007 ; Jin et al, 2008 ; Jo et al, 2008 ; Bleackley et al, 2011 ), Fe ( Wang et al, 2007 ; Jo et al, 2008 ; Bleackley et al, 2011 ), Mn ( Wang et al, 2007 ; Bleackley et al, 2011 ; Chesi et al, 2012 ), Co ( Bleackley et al, 2011 ), or Cr ( Jin et al, 2008 ; Johnson et al, 2016b ) and other stressors ( Bennett et al, 2001 ; Chang et al, 2002 ; Aouida et al, 2004 ; Serrano et al, 2004 ; Thorpe et al, 2004 ).…”

Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms

“…Cellular compartment and biological process analyses were performed with clusterProfiler [ 39 ] and evaluated for statistical significance (cut-off: p -value < 0.05). Clustering (heatmaps) was performed using the pheatmap package in R. Gd-sensitive and Gd-resistant mutants identified in the present study were compared with those from other screens carried out on yeast KO mutant libraries on Al [ 40 , 41 ], As [ 34 , 35 , 42 , 43 ], Cd [ 32 , 35 , 43 , 44 ], Co [ 45 ], Cr [ 35 , 46 ], Cu [ 33 , 35 , 45 , 47 ], Fe [ 33 , 45 , 47 ], Mn [ 45 , 47 , 48 ], La [ 49 ], Nd [ 50 ], Ni [ 32 , 45 , 51 ], Zn [ 35 , 45 , 47 , 52 ], Y [ 53 ], Yb [ 49 ] and other stressors [ 54 , 55 , 56 , 57 , 58 ]. When several independent studies performed similar screenings on the same stressor, the corresponding lists of mutants were combined.…”