Cargando…
Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms
Among the rare earth elements (REEs), a crucial group of metals for high-technologies. Gadolinium (Gd) is the only REE intentionally injected to human patients. The use of Gd-based contrasting agents for magnetic resonance imaging (MRI) is the primary route for Gd direct exposure and accumulation in...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459663/ https://www.ncbi.nlm.nih.gov/pubmed/37630673 http://dx.doi.org/10.3390/microorganisms11082113 |
_version_ | 1785097465773424640 |
---|---|
author | Grosjean, Nicolas Le Jean, Marie Ory, Jordan Blaudez, Damien |
author_facet | Grosjean, Nicolas Le Jean, Marie Ory, Jordan Blaudez, Damien |
author_sort | Grosjean, Nicolas |
collection | PubMed |
description | Among the rare earth elements (REEs), a crucial group of metals for high-technologies. Gadolinium (Gd) is the only REE intentionally injected to human patients. The use of Gd-based contrasting agents for magnetic resonance imaging (MRI) is the primary route for Gd direct exposure and accumulation in humans. Consequently, aquatic environments are increasingly exposed to Gd due to its excretion through the urinary tract of patients following an MRI examination. The increasing number of reports mentioning Gd toxicity, notably originating from medical applications of Gd, necessitates an improved risk–benefit assessment of Gd utilizations. To go beyond toxicological studies, unravelling the mechanistic impact of Gd on humans and the ecosystem requires the use of genome-wide approaches. We used functional deletomics, a robust method relying on the screening of a knock-out mutant library of Saccharomyces cerevisiae exposed to toxic concentrations of Gd. The analysis of Gd-resistant and -sensitive mutants highlighted the cell wall, endosomes and the vacuolar compartment as cellular hotspots involved in the Gd response. Furthermore, we identified endocytosis and vesicular trafficking pathways (ESCRT) as well as sphingolipids homeostasis as playing pivotal roles mediating Gd toxicity. Finally, tens of yeast genes with human orthologs linked to renal dysfunction were identified as Gd-responsive. Therefore, the molecular and cellular pathways involved in Gd toxicity and detoxification uncovered in this study underline the pleotropic consequences of the increasing exposure to this strategic metal. |
format | Online Article Text |
id | pubmed-10459663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104596632023-08-27 Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms Grosjean, Nicolas Le Jean, Marie Ory, Jordan Blaudez, Damien Microorganisms Article Among the rare earth elements (REEs), a crucial group of metals for high-technologies. Gadolinium (Gd) is the only REE intentionally injected to human patients. The use of Gd-based contrasting agents for magnetic resonance imaging (MRI) is the primary route for Gd direct exposure and accumulation in humans. Consequently, aquatic environments are increasingly exposed to Gd due to its excretion through the urinary tract of patients following an MRI examination. The increasing number of reports mentioning Gd toxicity, notably originating from medical applications of Gd, necessitates an improved risk–benefit assessment of Gd utilizations. To go beyond toxicological studies, unravelling the mechanistic impact of Gd on humans and the ecosystem requires the use of genome-wide approaches. We used functional deletomics, a robust method relying on the screening of a knock-out mutant library of Saccharomyces cerevisiae exposed to toxic concentrations of Gd. The analysis of Gd-resistant and -sensitive mutants highlighted the cell wall, endosomes and the vacuolar compartment as cellular hotspots involved in the Gd response. Furthermore, we identified endocytosis and vesicular trafficking pathways (ESCRT) as well as sphingolipids homeostasis as playing pivotal roles mediating Gd toxicity. Finally, tens of yeast genes with human orthologs linked to renal dysfunction were identified as Gd-responsive. Therefore, the molecular and cellular pathways involved in Gd toxicity and detoxification uncovered in this study underline the pleotropic consequences of the increasing exposure to this strategic metal. MDPI 2023-08-19 /pmc/articles/PMC10459663/ /pubmed/37630673 http://dx.doi.org/10.3390/microorganisms11082113 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Grosjean, Nicolas Le Jean, Marie Ory, Jordan Blaudez, Damien Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title | Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title_full | Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title_fullStr | Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title_full_unstemmed | Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title_short | Yeast Deletomics to Uncover Gadolinium Toxicity Targets and Resistance Mechanisms |
title_sort | yeast deletomics to uncover gadolinium toxicity targets and resistance mechanisms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459663/ https://www.ncbi.nlm.nih.gov/pubmed/37630673 http://dx.doi.org/10.3390/microorganisms11082113 |
work_keys_str_mv | AT grosjeannicolas yeastdeletomicstouncovergadoliniumtoxicitytargetsandresistancemechanisms AT lejeanmarie yeastdeletomicstouncovergadoliniumtoxicitytargetsandresistancemechanisms AT oryjordan yeastdeletomicstouncovergadoliniumtoxicitytargetsandresistancemechanisms AT blaudezdamien yeastdeletomicstouncovergadoliniumtoxicitytargetsandresistancemechanisms |