Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials
Roger M. Pallares, David Faulkner, Dahlia D. An, Solène Hébert, Alex Loguinov, Michael Proctor, Jonathan A. Villalobos, Kathleen A. Bjornstad, Chris J. Rosen, Chris D. Vulpe, Rebecca J. Abergel
Abstract
strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein-protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.