Valeria C. Culotta, Ph.D.
Johns Hopkins University
NIEHS Grant P30ES003819
An NIEHS-supported study reports that an enzyme important in protecting cells from free radicals also helps repress respiration in rapidly dividing cells. The results reveal how yeast and cancer cells may repress respiration in favor of aerobic glycolysis, or fermentation, to promote rapid growth.
The researchers studied Cu/Zn superoxide dismutase (SOD1), which is known to help protect cells against oxidative stress. Using the yeast Saccharomyces cerevisiae, they revealed a new function for SOD1 in repressing respiration. When glucose and reactive oxygen are present, the enzyme binds to the casein kinase 1-gamma homologs Yck1p and Yck2p, protecting them from degradation. Yck1p and Yck2p are essential for respiratory repression, as well as nutrient sensing. Together, oxygen, glucose, and reactive oxygen make up a single circuit that can repress respiration through SOD1/casein kinase signaling. These results suggest that SOD1 acts as a metabolic focal point for integrating oxygen, nutrients (glucose), and reactive oxygen to direct energy metabolism.
Citation: Reddi AR, Culotta VC. 2013. SOD1 integrates signals from oxygen and glucose to repress respiration. Cell 152(1-2):224-235.