Abstract
Zinc is an essential trace element that is required for the function of a large number of proteins. As these zinc-binding proteins are found within the cytosol and organelles, all eukaryotes require mechanisms to ensure that zinc is delivered to organelles, even under conditions of zinc deficiency. Although many zinc transporters belonging to the Cation Diffusion Facilitator (CDF) families have well characterized roles in transporting zinc into the lumens of intracellular compartments, relatively little is known about the mechanisms that maintain organelle zinc homeostasis. The fission yeast Schizosaccharomyces pombe is a useful model system to study organelle zinc homeostasis as it expresses three CDF family members that transport zinc out of the cytosol into intracellular compartments: Zhf1, Cis4, and Zrg17. Zhf1 transports zinc into the endoplasmic reticulum, and Cis4 and Zrg17 form a heterodimeric complex that transports zinc into the cis-Golgi. Here we have used the high and low affinity ZapCY zinc-responsive FRET sensors to examine cytosolic zinc levels in yeast mutants that lack each of these CDF proteins. We find that deletion of cis4 or zrg17 leads to higher levels of zinc accumulating in the cytosol under conditions of zinc deficiency, whereas deletion of zhf1 results in zinc accumulating in the cytosol when zinc is not limiting. We also show that the expression of cis4, zrg17, and zhf1 is independent of cellular zinc status. Taken together our results suggest that the Cis4/Zrg17 complex is necessary for zinc transport out of the cytosol under conditions of zinc-deficiency, while Zhf1 plays the dominant role in removing zinc from the cytosol when labile zinc is present. We propose that the properties and/or activities of individual CDF family members are fine-tuned to enable cells to control the flux of zinc out of the cytosol over a broad range of environmental zinc stress.
Highlights
Zinc is an essential trace metal that is required for the structure and activity of a large number of proteins
Much is known about the mechanisms that control cytosolic zinc levels, relatively little is known about the mechanisms that maintain organelle zinc homeostasis
As proteins belonging to the Cation Diffusion Facilitator (CDF) family transport zinc into organelles, here we used a fission yeast model system to determine if the expression or function of zinc transporters belonging to this family was regulated by zinc
Summary
Zinc is an essential trace metal that is required for the structure and activity of a large number of proteins. In eukaryotes these proteins include transcription factors containing structural domains stabilized by zinc ions, such as the C2H2-type and C4-type zinc fingers [1]. Due to the essential nature of some of these proteins, all organisms are challenged with obtaining sufficient levels of zinc for incorporation into newly synthesized proteins. A further complicating factor is that excessive levels of zinc are toxic to cells. Zinc acquisition, compartmentalization, storage, and efflux need to be tightly regulated to maintain zinc at a level that is sufficient, but not toxic to cell metabolism
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