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PhD Dissertation 01072015 Final.pdf (4.68 MB)

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Understanding mechanisms of zinc homeostasis in Schizosaccharomyces pombe

Choi, Sang Yong
http://rave.ohiolink.edu/etdc/view?acc_num=osu1420599754

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Human Ecology: Human Nutrition.
Zinc is essential for cell growth, but can be toxic when in excess. As a consequence, intracellular zinc levels are tightly controlled by complex mechanisms that maintain zinc homeostasis in all biological creatures. In eukaryotic cells, factors that affect zinc homeostasis include zinc transporters, zinc buffering molecules, and zinc-regulatory factors. The levels of these factors are precisely regulated to maintain optimal intracellular zinc levels. To extend the growing literature in the roles of genes involved in zinc homeostasis, this dissertation investigates the role of the above executants in maintaining cytosolic zinc levels in Schizosaccharomyces pombe. In S. pombe, Loz1 plays a specific role in repressing gene expression when zinc is in excess. In zinc-replete conditions, Loz1 down-regulates zrt1, a gene encoding a high affinity zinc uptake transporter, and indirectly up-regulates zym1 expression, a gene which encodes a zinc metallothionein. Deletion of Loz1, thus, causes constitutive zrt1 expression and low zym1 expression. In addition, cells lacking a functional loz1 gene hyperaccumulate zinc in zinc-rich medium. In chapters 2 and 3, I take advantage of the loz1 mutation, and other yeast mutants to determine the roles of specific zinc transporters and zinc buffering molecules in maintaining zinc levels in the cytosol. Specifically, I utilize genetically encoded zinc-responsive FRET-based sensors, which allow changes in the labile pool of cytosolic labile zinc to be measured. My results show that Zhf1, a zinc transporter in endoplasmic reticulum membrane, and Zrg17 and Cis4, which reside in Golgi membrane, play a role in maintaining the cytosolic labile zinc pools upon a zinc shock. In addition, my works describe how Loz1 controls zinc homeostasis in zinc-replete conditions and reveal that phytochelatins, small molecules that have a well-known role in the detoxification of toxic heavy metals, also have an important zinc buffering role. In chapters 4 and 5, I investigate the molecular mechanisms by which zinc-responsive transcription factors are regulated by zinc. Using chimeric proteins containing Loz1, this study examines the accessory domain adjacent to a double zinc finger, and shows that it is necessary for Loz1-mediated zinc-responsive changes in gene expression. This dissertation provides a platform for the understanding of zinc homeostasis mechanisms in fission yeast by examining the role that specific zinc transporters, zinc buffering molecules, and the zinc-regulated factor Loz1 play in regulating cellular zinc levels. The results suggest that specific zinc transporters and Loz1 control the labile zinc pool in cells. Also, the roles of phytochelatins are highlighted as zinc buffering molecules. This discovery extends the current knowledge of how zinc buffering molecules influence metal homeostasis. While a number of zinc transporters have been identified in various eukaryotic cells, the zinc buffering molecules that modify the labile zinc pool remain to be further investigated.
Amanda Bird (Advisor)
206 p.
Nutrition

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Citations

  • Choi, S. Y. (2015). Understanding mechanisms of zinc homeostasis in Schizosaccharomyces pombe [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1420599754

    APA Style (7th edition)

  • Choi, Sang Yong. Understanding mechanisms of zinc homeostasis in Schizosaccharomyces pombe. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1420599754.

    MLA Style (8th edition)

  • Choi, Sang Yong. "Understanding mechanisms of zinc homeostasis in Schizosaccharomyces pombe." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1420599754

    Chicago Manual of Style (17th edition)

osu1420599754
279
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This open access ETD is published by The Ohio State University and OhioLINK.