Homeostatic and adaptive responses to zinc deficiency in Saccharomyces cerevisiae

Abstract

Zinc is an essential nutrient and serves as a structural or catalytic cofactor for many proteins. Thus, cells need mechanisms to maintain zinc homeostasis when available zinc supplies decrease. In addition, cells require other mechanisms to adapt intracellular processes to suboptimal levels of zinc. By exploring the transcriptional responses to zinc deficiency, studies of the yeast Saccharomyces cerevisiae have revealed both homeostatic and adaptive responses to low zinc. The Zap1 zinc-responsive transcription factor regulates several genes in yeast, and the identity of these genes has led to new insights regarding how cells respond to the stress of zinc deficiency.

FIGURE 1.

Anatomy of the Zap1 transcription factor. In A, the zinc fingers of Zap1 are shown by the filled boxes, and AD1 and AD2 are indicated by the hatched boxes. The potential zinc ligands at the ends of ZRD^AD1 are in boldface and underlined. In B, a model of the folded form of the ZF1/ZF2 finger pair is shown. Zinc atoms are cyan, the zinc ligands are blue, and the residues lining the hydrophobic interface between the fingers are red.

FIGURE 2.

Transcriptional responses to zinc deficiency mediated by Zap1. The subcellular location and functional role of the protein products of known or likely Zap1 target genes are shown. Gene products shown in yellow represent those that are up-regulated by Zap1, and those in blue indicate down-regulated proteins. The symbol for Zrt2 is split because that gene is both activated and repressed by Zap1. Gray circles indicate gene products not regulated by zinc. PM, plasma membrane; MITO, mitochondria; ORF, open reading frame.

FIGURE 3.

Mechanisms of ZRT2 (A) and ADH1 (B) repression mediated by Zap1. TATA elements (filled circles), transcription factor-binding sites (filled rectangles), and RNAs produced (arrows) are shown.