Excess copper causes repression of global translation in Saccharomyces cerevisiae

Abstract

Abstract Copper is an essential cofactor for numerous metabolic pathways; however, excess intracellular copper is cytotoxic. In this study, we investigated the consequences of deregulated Cu + uptake mediated by the high-affinity copper transporter Ctr1 in the model yeast Saccharomyces cerevisiae . Constitutive expression of a carboxy-terminally truncated Ctr1 variant, CTR1(300) , resulted in elevated intracellular copper levels, increased oxidative stress, and reduced oxygen consumption, likely due to impairment of iron-sulfur cluster-containing proteins. Notably, CTR1(300) -expressing cells exhibited a pronounced repression of global protein synthesis at very low copper concentrations, a phenotype that was recapitulated in wild-type cells when exposed to higher copper levels. These findings reveal that excessive Cu + accumulation negatively impacts cellular respiration and translation, identifying protein synthesis as a sensitive target of copper toxicity.