Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive phenotypes of yeast lacking CuZnSOD.
Yeasts lacking copper-zinc superoxide dismutase (sod1Delta) exhibit a broad range of phenotypes, many of which can be rescued by growth in the presence of high levels of ionic manganese. We undertook a comprehensive survey of the effects of manganese on wild-type and sod1Delta yeasts and found that 5 mM Mn2+ rescued all known growth-related phenotypes, such as slow growth in air, temperature sensitivity, specific amino acid auxotrophies, no growth in high oxygen, poor growth in nonfermentable carbon sources, and decreased stationary-phase survival. Iron-related phenotypes-elevated electron paramagnetic resonance detectable ("free") iron, decreased aconitase activity, and fragmenting vacuoles-as well as zinc sensitivity were also rescued. The activity of manganese superoxide dismutase remained constant or was reduced when the yeasts were grown in the presence of MnCl2, indicating that induction of this alternative superoxide dismutase is not the explanation. In contrast to MnCl2 treatment, addition of two manganese-containing superoxide dismutase mimetic compounds to the growth medium did not provide any rescue of sod1Delta yeast growth but rather had an sod1Delta-selective inhibitory effect at micromolar concentrations. Mechanisms by which ionic manganese can effect this rescue, while the mimetic compounds do not, are discussed.
Sanchez
Raylene J
RJ
Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive, East, Los Angeles, CA 90095-1569, USA.
Srinivasan
Chandra
C
Munroe
William H
WH
Wallace
Matthew Alan
MA
Martins
Jacob
J
Kao
Tina Y
TY
Le
Kate
K
Gralla
Edith Butler
EB
Valentine
Joan Selverstone
JS
D004578:Electron Spin Resonance Spectroscopy; D017353:Gene Deletion; D007501:Iron / Q000032:analysis / Q000378:metabolism; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014617:Vacuoles / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology
D029701:Saccharomyces cerevisiae Proteins; D008345:Manganese; D007501:Iron; D013482:Superoxide Dismutase; D015032:Zinc; D010100:Oxygen