Dr. Amit Reddi, Johns Hopkins University

A New Role for An Old Copper Enzyme in Glucose and Oxygen Sensing

Cu/Zn superoxide dismutase (SOD1) is a highly abundant SOD in eukaryotic cells and is in the frontline of defense against reactive oxygen species (ROS) by catalyzing the disproportionation of superoxide radicals into hydrogen peroxide and oxygen. Using the baker’s yeast (Saccharomyces cerevisiae) as a model organism, we now report a new role for SOD1 in transmitting signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologues required for respiratory repression. SOD1 binds a C-terminal degron identified in yeast CK1γ and promotes kinase stability by catalyzing superoxide conversion to peroxide. Our findings suggest that while the bulk of SOD1 is dispensable for antioxidant defense, it is required for metabolic control using signals from superoxide produced during aerobic glycolysis. Thus, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/ CK1γ signaling.

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