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Chemical-genomic profiling identifies genes that protect yeast from aluminium, gallium, and indium toxicity
University of Gothenburg, Sweden; University of Geneva, Switzerland.
RISE Research Institutes of Sweden, Bioekonomi och hälsa, Bioraffinaderi och energi. University of Gothenburg, Sweden.ORCID-id: 0000-0003-1914-5130
University of Gothenburg, Sweden.
Bibliothèque Nationale du Luxembourg, Luxembourg.
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2023 (Engelska)Ingår i: Metallomics, ISSN 1756-5901, E-ISSN 1756-591X, Vol. 15, nr 6, artikel-id mfad032Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Aluminium, gallium, and indium are group 13 metals with similar chemical and physical properties. While aluminium is one of the most abundant elements in the Earth's crust, gallium and indium are present only in trace amounts. However, the increased use of the latter metals in novel technologies may result in increased human and environmental exposure. There is mounting evidence that these metals are toxic, but the underlying mechanisms remain poorly understood. Likewise, little is known about how cells protect themselves from these metals. Aluminium, gallium, and indium are relatively insoluble at neutral pH, and here we show that they precipitate in yeast culture medium at acidic pH as metal-phosphate species. Despite this, the dissolved metal concentrations are sufficient to induce toxicity in the yeast Saccharomyces cerevisiae. By chemical-genomic profiling of the S. cerevisiae gene deletion collection, we identified genes that maintain growth in the presence of the three metals. We found both shared and metal-specific genes that confer resistance. The shared gene products included functions related to calcium metabolism and Ire1/Hac1-mediated protection. Metal-specific gene products included functions in vesicle-mediated transport and autophagy for aluminium, protein folding and phospholipid metabolism for gallium, and chorismate metabolic processes for indium. Many of the identified yeast genes have human orthologues involved in disease processes. Thus, similar protective mechanisms may act in yeast and humans. The protective functions identified in this study provide a basis for further investigations into toxicity and resistance mechanisms in yeast, plants, and humans. © 2023 The Author(s). 

Ort, förlag, år, upplaga, sidor
Oxford University Press , 2023. Vol. 15, nr 6, artikel-id mfad032
Nyckelord [en]
aluminium, chemical-genomic profiling, gallium, indium, toxicity, yeast, Aluminum, Cell death, Environmental technology, Genes, Metabolism, Phospholipids, Trace elements, aluminum sulfate, calcium ion, chorismic acid, gallium chloride, indium chloride, protein IRE1, Chemical and physical properties, Earth's crust, Environmental exposure, Gene products, Genomics, Human exposures, Neutral pH, Trace amounts, Yeast culture, aluminum overload, Article, autophagy (cellular), calcium metabolism, cell proliferation, chemical fingerprinting, controlled study, fungal cell culture, fungal strain, fungus growth, gene deletion, gene knockout, gene product, genetic profile, metal poisoning, nonhuman, phospholipid metabolism, precipitation, protein folding, Saccharomyces cerevisiae, yeast cell, Genome
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:ri:diva-65686DOI: 10.1093/mtomcs/mfad032Scopus ID: 2-s2.0-85163076831OAI: oai:DiVA.org:ri-65686DiVA, id: diva2:1786784
Anmärkning

This work was supported by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas: grant number 942-2015-376) to M.J.T., by the European Cooperation in Science and Technology COST Action TD1407 NOTICE (Network on Technology-Critical Elements—TCEs) to M.F. and M.J.T, and by the mobility grant Short Term Scientific Missions (STSM) within the EU COST Action TD1407—NOTICE and the University of Geneva to Y.S.

Tillgänglig från: 2023-08-10 Skapad: 2023-08-10 Senast uppdaterad: 2024-05-15Bibliografiskt granskad

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