Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase.
Mutants of Saccharomyces cerevisiae lacking a functional SOD1 gene encoding Cu/Zn superoxide dismutase (SOD) are sensitive to atmospheric levels of oxygen and are auxotrophic for lysine and methionine when grown in air. We have previously shown that these defects of SOD-deficient yeast cells can be overcome through mutations in either the BSD1 or BSD2 (bypass SOD defects) gene. In this study, the wild-type allele of BSD1 was cloned by functional complementation and was physically mapped to the left arm of chromosome VII. BSD1 is identical to PMR1, encoding a member of the P-type ATPase family that localizes to the Golgi apparatus. PMR1 is thought to function in calcium metabolism, and we provide evidence that PMR1 also participates in the homeostasis of manganese ions. Cells lacking a functional PMR1 gene accumulate elevated levels of intracellular manganese and are also extremely sensitive to manganese ion toxicity. We demonstrate that mutations in PMR1 bypass SOD deficiency through a mechanism that depends on extracellular manganese. Collectively, these findings indicate that oxidative damage in a eukaryotic cell can be prevented through alterations in manganese homeostasis.
Lapinskas
P J
PJ
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Cunningham
K W
KW
Liu
X F
XF
Fink
G R
GR
Culotta
V C
VC
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000332:Aerobiosis; D000693:Anaerobiosis; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D005838:Genotype; D008239:Lysine / Q000378:metabolism; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D016296:Mutagenesis; D010100:Oxygen / Q000633:toxicity*; D010269:Paraquat / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D013489:Suppression, Genetic; D015032:Zinc / Q000378:metabolism
D008345:Manganese; D008715:Methionine; D013482:Superoxide Dismutase; D000251:Adenosine Triphosphatases; D015032:Zinc; D008239:Lysine; D010269:Paraquat; D010100:Oxygen; D002118:Calcium