The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of manganese ions

Paula Jean Lapinskas, Su Ju Lin, Valeria Cizewski Culotta

Research output: Contribution to journalArticle

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Abstract

We previously reported that oxidative damage in yeast lacking copper/zinc superoxide dismutase (SOD1) can be alleviated through mutations in PMR1, encoding a calcium P-type ATPase homologue that also functions in manganese homeostasis. In an attempt to further understand the relationship between manganese ions, PMR1 and SOD1, we conducted a search for manganese homeostasis genes that interact with PMR1. A genomic library was screened for genes that, when overexpressed, suppress the manganese hypersensitivity associated with pmr1 mutations. A single clone was isolated that reduced manganese toxicity in both the pmr1 mutant and PMR1 wild-type yeast. This gene was identified as CCC1, previously shown to function in calcium metabolism. Our studies indicate that, like PMR1, CCC1 functions in the homeostasis of both calcium and manganese ions. The Ccc1p polypeptide was found to localize to a Golgi-like organelle in yeast cells. Ccc1p co- fractionated with a Golgi marker in subcellular fractionation studies and, with immunofluorescence microscopy, Ccc1p exhibited a punctate pattern of staining typical of yeast Golgi. Our studies suggest that Ccc1p may act to sequester manganese ions in this organelle and limit the intracellular availability of the metal. First, overexpression of CCC1 reduced manganese cytotoxicity without lowering total accumulation of the metal. Second, overexpression of CCC1 appeared to limit the intracellular availability of the manganese ions needed to support aerobic growth of SOD1 mutants. We provide a model in which Ccc1p and Pmr1p work together to control the intracellular partitioning of manganese ions.

Original languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalMolecular Microbiology
Volume21
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

Manganese
Saccharomyces cerevisiae
Homeostasis
Ions
Genes
Yeasts
Organelles
Metals
Calcium
Mutation
Genomic Library
Calcium-Transporting ATPases
Fluorescence Microscopy
Superoxide Dismutase
Zinc
Copper
Hypersensitivity
Clone Cells
Staining and Labeling
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Lapinskas, P. J., Lin, S. J., & Culotta, V. C. (1996). The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of manganese ions. Molecular Microbiology, 21(3), 519-528.

The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of manganese ions. / Lapinskas, Paula Jean; Lin, Su Ju; Culotta, Valeria Cizewski.

In: Molecular Microbiology, Vol. 21, No. 3, 1996, p. 519-528.

Research output: Contribution to journalArticle

Lapinskas, PJ, Lin, SJ & Culotta, VC 1996, 'The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of manganese ions', Molecular Microbiology, vol. 21, no. 3, pp. 519-528.
Lapinskas, Paula Jean ; Lin, Su Ju ; Culotta, Valeria Cizewski. / The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of manganese ions. In: Molecular Microbiology. 1996 ; Vol. 21, No. 3. pp. 519-528.
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