JBIC Journal of Biological Inorganic Chemistry

, Volume 15, Issue 7, pp 1051–1062

The effect of phosphate accumulation on metal ion homeostasis in Saccharomyces cerevisiae

  • Leah Rosenfeld
  • Amit R. Reddi
  • Edison Leung
  • Kimberly Aranda
  • Laran T. Jensen
  • Valeria C. Culotta
Original Paper

DOI: 10.1007/s00775-010-0664-8

Cite this article as:
Rosenfeld, L., Reddi, A.R., Leung, E. et al. J Biol Inorg Chem (2010) 15: 1051. doi:10.1007/s00775-010-0664-8

Abstract

Much of what is currently understood about the cell biology of metals involves their interactions with proteins. By comparison, little is known about interactions of metals with intracellular inorganic compounds such as phosphate. Here we examined the role of phosphate in metal metabolism in vivo by genetically perturbing the phosphate content of Saccharomycescerevisiae cells. Yeast pho80 mutants cannot sense phosphate and have lost control of phosphate uptake, storage, and metabolism. We report here that pho80 mutants specifically elevate cytosolic and nonvacuolar levels of phosphate and this in turn causes a wide range of metal homeostasis defects. Intracellular levels of the hard-metal cations sodium and calcium increase dramatically, and cells become susceptible to toxicity from the transition metals manganese, cobalt, zinc, and copper. Disruptions in phosphate control also elicit an iron starvation response, as pho80 mutants were seen to upregulate iron transport genes. The iron-responsive transcription factor Aft1p appears activated in cells with high phosphate content in spite of normal intracellular iron levels. The high phosphate content of pho80 mutants can be lowered by mutating Pho4p, the transcription factor for phosphate uptake and storage genes. Such lowering of phosphate content by pho4 mutations reversed the high calcium and sodium content of pho80 mutants and prevented the iron starvation response. However, pho4 mutations only partially reversed toxicity from heavy metals, representing a novel outcome of phosphate dysregulation. Overall, these studies underscore the importance of maintaining a charge balance in the cell; a disruption in phosphate metabolism can dramatically impact on metal homeostasis.

Keywords

Yeast Manganese Aft1 Pho80 Polyphosphate 

Abbreviations

cDNA

Complementary DNA

FC

Fold change

ICP-MS

Inductively coupled plasma mass spectroscopy

mRNA

Messenger RNA

OD600 nm

Optical density at 600 nm

YPD

1% Bacto yeast extract, 2% Bacto peptone, 2% dextrose

Supplementary material

775_2010_664_MOESM1_ESM.pdf (134 kb)
Supplementary material 1 (PDF 133 kb)

Copyright information

© SBIC 2010

Authors and Affiliations

  • Leah Rosenfeld
    • 1
  • Amit R. Reddi
    • 1
  • Edison Leung
    • 1
  • Kimberly Aranda
    • 1
  • Laran T. Jensen
    • 1
    • 2
  • Valeria C. Culotta
    • 1
  1. 1.Department of Environmental Health SciencesJohns Hopkins University Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Department of Biochemistry, Faculty of ScienceMahidol UniversityBangkokThailand

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