Fecha de publicación: -- Fuente: PubMed "wine" Biometals. 2026 Nov 6. doi: 10.1007/s10534-026-00905-8. Online ahead of print.ABSTRACTCopper is essential for life as an enzymatic cofactor and antioxidant participant, but in excess, it is toxic to all living organisms, including yeast. Because this toxicity varies by genetic background, we investigated the underlying modifier loci using a panel of four genetically diverse strains-Sake (SA), North American (NA), West African (WA), and Wine/European (WE)-and their segregants. Copper sulfate (CuSO4) susceptibility, quantified by the maximum growth rate (µMax), was strain-dependent, with resistance decreasing in the order SA > WE > WA > NA. Furthermore, cellular growth was inversely correlated with intracellular superoxide levels measured via dihydroethidium staining. By analyzing µMax in 96 segregants from an SA x NA cross exposed to CuSO4, we performed quantitative trait locus (QTL) mapping and prioritized 16 candidate modifiers. Functional validations in a Yhk8 deletant resulted in impaired growth and elevated superoxide levels upon copper exposure. Finally, bioinformatics structural predictions support that Yhk8 is a putative drug/proton antiporter with functional analogy to human SLC47A1, containing a predicted copper-binding site. Together, these findings support Yhk8 as a key genetic modifier of copper response in yeast.PMID:42993454 | DOI:10.1007/s10534-026-00905-8