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 only REE intentionally injected to human patients. The use Gd-based contrasting agents magnetic resonance imaging (MRI) primary route Gd direct exposure and accumulation in humans. Consequently, aquatic environments are increasingly exposed due its excretion through urinary tract patients following an MRI examination. increasing number reports mentioning toxicity, notably originating from medical applications Gd, necessitates improved risk–benefit assessment utilizations. To go beyond toxicological studies, unravelling mechanistic impact on humans ecosystem requires genome-wide approaches. We used functional deletomics, robust method relying screening knock-out mutant library Saccharomyces cerevisiae toxic concentrations Gd. analysis Gd-resistant -sensitive mutants highlighted cell wall, endosomes vacuolar compartment as cellular hotspots involved response. Furthermore, we identified endocytosis vesicular trafficking pathways (ESCRT) well sphingolipids homeostasis playing pivotal roles mediating toxicity. Finally, tens yeast genes with orthologs linked renal dysfunction were Gd-responsive. Therefore, molecular toxicity detoxification uncovered this study underline pleotropic consequences strategic metal.