Genome-wide screening of yeast metal homeostasis genes involved in mitochondrial functions.

ABSTRACT

Metal ions are essential for mitochondria to execute their roles. Yeast mutants that are sensitive to metals (either excess or deficiency) on non-fermentable media but not on fermentable media may carry mutations in genes that participate in metal homeostasis involving mitochondrial functions. A collection of approximately 4,800 haploid yeast deletion mutants was screened for metal ion homeostasis genes linked to mitochondrial respiration. In addition to several well-characterized metal homeostasis genes, 45 new mutants, impaired in various molecular functions, were identified on non-fermentable media that were sensitive to adscititious metals or metal deficiency. While 35 of these mutants displayed metal-sensitivity only on non-fermentable media, the remaining 10 also exhibited metal sensitivity on fermentable media, suggesting metal-sensitivity of the latter is not due to mitochondrial dysfunction. Inductively coupled plasma optical emission spectrometry (ICP-OES) was conducted for 12 mutants that were sensitive to metal excess to analyze their metal contents. Among these 12 mutants 7 were sensitive to metal excess on non-fermentable but not on fermentable media. All the seven respiration-dependent mutants displayed abnormal levels of metal ions inside mitochondria, indicative of disrupted mitochondrial metal homeostasis. This study therefore effectively identified multiple new genes involved in metal homeostasis pathways possibly pertinent to mitochondrial functions, and should be helpful for future studies to further understand their molecular roles.