Homeostatic and Adaptive Responses to Zinc Deficiency in Saccharomyces cerevisiae

David J Eide

doi:10.1074/jbc.r900014200

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.

Highlights

Homeostatic Responses to Zinc DeficiencyFirst among Zap1-mediated responses to zinc deficiency is the autoregulation of the ZAP1 gene itself [2]
In Saccharomyces cerevisiae, Zap1 is the central player in the response to zinc deficiency [1]
We have shown that ZRC1 induction is a novel “proactive” mechanism of zinc homeostasis [26]

Summary

Homeostatic Responses to Zinc Deficiency

First among Zap1-mediated responses to zinc deficiency is the autoregulation of the ZAP1 gene itself [2]. Under severe deficiency, when Zap levels rise due to autoregulation, Zap binds to ZRE3 and blocks ZRT2 expression. This pattern of expression ensures that the low affinity Zrt transporter is not expressed at times when it is unable to contribute to zinc uptake. Under zinc-limiting conditions, expression of the ZRT3 gene is up-regulated by Zap1 [24]. Because zinc-limited cells express high levels of zinc transporters like Zrt, they are poised to accumulate substantial amounts of zinc should it become available. We refer to this condition as “zinc shock.”. Induction of Uth may aid the degradation of mitochondria in zinc-limited cells, and these mitochondria could be a source of zinc for other purposes

Adaptive Responses to Zinc Deficiency

Conclusions