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PMID:8367458

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Citation

Tamai, KT, Gralla, EB, Ellerby, LM, Valentine, JS and Thiele, DJ (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 90:8013-7

Abstract

Copper-zinc superoxide dismutase catalyzes the disproportionation of superoxide anion to hydrogen peroxide and dioxygen and is thought to play an important role in protecting cells from oxygen toxicity. Saccharomyces cerevisiae strains lacking copper-zinc superoxide dismutase, which is encoded by the SOD1 gene, are sensitive to oxidative stress and exhibit a variety of growth defects including hypersensitivity to dioxygen and to superoxide-generating drugs such as paraquat. We have found that in addition to these known phenotypes, SOD1-deletion strains fail to grow on agar containing the respiratory carbon source lactate. We demonstrate here that expression of the yeast or monkey metallothionein proteins in the presence of copper suppresses the lactate growth defect and some other phenotypes associated with SOD1-deletion strains, indicating that copper metallothioneins substitute for copper-zinc superoxide dismutase in vivo to protect cells from oxygen toxicity. Consistent with these results, we show that yeast metallothionein mRNA levels are dramatically elevated under conditions of oxidative stress. Furthermore, in vitro assays demonstrate that yeast metallothionein, purified or from whole-cell extracts, exhibits copper-dependent antioxidant activity. Taken together, these data suggest that both yeast and mammalian metallothioneins may play a direct role in the cellular defense against oxidative stress by functioning as antioxidants.

Links

PubMed PMC47278

Keywords

Animals; Antioxidants/metabolism; Cloning, Molecular; Copper/pharmacology; Gene Deletion; Genes, Fungal; Haplorhini; Lactates/metabolism; Metallothionein/genetics; Metallothionein/metabolism; Plasmids; RNA, Messenger/metabolism; Recombinant Fusion Proteins/metabolism; Restriction Mapping; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/growth & development; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:MTCU2

enables

GO:0016209: antioxidant activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:MTCU2

involved_in

GO:0019430: removal of superoxide radicals

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:MTCU2

involved_in

GO:0019430: removal of superoxide radicals

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000003865

P

Seeded From UniProt

complete

YEAST:MTCU2

enables

GO:0004784: superoxide dismutase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:MTCU1

involved_in

GO:0019430: removal of superoxide radicals

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:MTCU1

enables

GO:0016209: antioxidant activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:MTCU1

enables

GO:0004784: superoxide dismutase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:MTCU1

involved_in

GO:0019430: removal of superoxide radicals

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000003865

P

Seeded From UniProt

complete


See also

References

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