Yeast lacking Cu-Zn superoxide dismutase show altered iron homeostasis. Role of oxidative stress in iron metabolism.

Saccharomyces cerevisiae lacking copper-zinc superoxide dismutase (sod1) shows a series of defects, including reduced rates of aerobic growth in synthetic glucose medium and reduced ability to grow by respiration in glycerol-rich medium. In this work, we observed that addition of iron improved the respiratory growth of the sod1 mutant and in glucose medium total intracellular iron content was higher in the sod1 mutant than in wild type cells. Transcription of the high affinity iron transporter gene, FET3, was enhanced in the sod1 mutant, suggesting that iron transport systems were up-regulated. An sod1/fet3 double mutant showed increased sensitivity to oxygen and increased transcription of FET4, an alternative, low affinity, iron transporter. We propose that this increased iron demand in the sod1 mutant may be a reflection of the cells' efforts to reconstitute iron-sulfur cluster-containing enzymes that are continuously inactivated in conditions of excess superoxide.