Yeast flavohemoglobin is upregulated by reactive oxygen species and protects SOD mutants from nitrosative stress

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1452-A1452
• Main Authors: O'Brien, Kristin, Tawney, Rachel, Smith, Lisa
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1452-a

Yeast flavohemoglobin (YHb) is a nitric‐oxide oxidoreductase expressed in Saccharomyces cerevisiae. Previous studies have shown that YHb protects cells against nitrosative stress, but its role in protecting cells against oxidative stress is controversial. Mutants lacking superoxide dismutase (SOD1 and SOD2) have approximately seven‐fold higher levels of YHb compared to wild‐type cells. Levels of YHb in sod1/ sod2 mutants are reduced to that of wild‐type cells when sod1/sod2 mutants are treated with the antioxidant glutathione. Surprisingly however, mutants lacking YHb1, SOD1 and SOD2 show enhanced growth rates, and reduced levels of protein oxidation compared to mutants lacking only SOD1 and SOD2. High levels of YHb in sod1/sod2 mutants may be important for protecting these mutants from enhanced nitrosative stress, as these cells are more sensitive to the NO‐donor DETA‐NO compared to wild‐type cells. Similarly, respiring wild‐type cells that are producing reactive oxygen species (ROS) from the respiratory chain, are more sensitive to DETA‐NO compared to fermenting cells. Together these data suggest that elevated levels of ROS induce the expression of YHb required to protect cells against an increased sensitivity to nitrosative stress when ROS levels are increased. Supported by the American Heart Association (Beginning Grant‐in‐Aid) to KOB.