Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles

Su Ju Lin, Valeria Cizewski Culotta

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Oxygen toxicity in Saccharomyces cerevisiae lacking the copper/zinc superoxide dismutase (SOD1) can be suppressed by overexpression of the S. cerevisiae ATX2 gene. Multiple copies of ATX2 were found to reverse the aerobic auxotrophies of sod1Δ mutants for lysine and methionine and also to enhance the resistance of these yeast strains to paraquat and atmospheric levels of oxygen. ATX2 encodes a novel 34.4-kDa polypeptide with a number of potential membrane-spanning domains. Our studies indicate that Atx2p localizes to the membrane of a vesicular compartment in yeast cells reminiscent of the Golgi apparatus. With indirect immunofluorescence microscopy, Atx2p exhibited a punctate pattern of staining typical of the Golgi apparatus, and upon subcellular fractionation, Atx2p colocalized with a biochemical marker for the yeast Golgi apparatus. We demonstrate here that this vesicle protein normally functions in the homeostasis of manganese ions and that this role in metal metabolism is necessary for the ATX1 suppression of SOD1 deficiency. First, overexpression of ATX2 caused cells to accumulate increased levels of manganese. Second, a deletion in ATX2 caused a decrease in the apparent available level of intracellular manganese and caused sod1Δ mutants to become dependent upon exogenous manganese for aerobic growth. Third, ATX2 was incapable of suppressing oxidative damage in cells depleted of manganese ions or lacking the plasma membrane transporter for manganese. The effect of ATX2 overexpression on manganese accumulation and oxygen resistance is similar to what we have previously reported for mutations in PMR1, which encodes a manganese-trafficking protein that also resides in a vesicular compartment. Our studies are consistent with a model in which Atx2p and Pmr1p work in opposite directions to control manganese homeostasis.

Original languageEnglish (US)
Pages (from-to)6303-6312
Number of pages10
JournalMolecular and Cellular Biology
Volume16
Issue number11
StatePublished - 1996
Externally publishedYes

Fingerprint

Protein Transport
Manganese
Saccharomyces cerevisiae
Golgi Apparatus
Yeasts
Oxygen
Homeostasis
Ions
Paraquat
Membrane Transport Proteins
Indirect Fluorescent Antibody Technique
Fluorescence Microscopy
Methionine
Membrane Potentials
Lysine
Superoxide Dismutase
Zinc
Copper
Biomarkers
Metals

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles. / Lin, Su Ju; Culotta, Valeria Cizewski.

In: Molecular and Cellular Biology, Vol. 16, No. 11, 1996, p. 6303-6312.

Research output: Contribution to journalArticle

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