"Cu/Zn Superoxide Dismutase (SOD1) Regulates Aerobic Glycolysis: Implications for Cancer Metabolism"

Amit R. Reddi, PhD
Assistant Professor
School of Chemistry & Biochemistry
Georgia Tech

The shift in energy metabolism away from respiration towards fermentation is a hallmark of cancer and is required to meet the metabolic demands of proliferating cells. Mutations that lead to defects in the ability to sense and metabolize oxygen and glucose, two essential nutrients that control energy metabolism, often lead to the initiation of a large number of cancers. However, the molecular mechanisms that connect nutrient availability to control of respiratory vs. fermentative metabolism are complex and not fully understood. Largely using the eukaryotic model organism Baker’s yeast (Saccharomyces cerevisiae), we demonstrate that the enzyme, Cu/Zn Superoxide Dismutase (SOD1), acts as a metabolic focal point for integrating oxygen and glucose availability to control of energy metabolism. When glucose and oxygen are present, SOD1 stabilizes a casein kinase, casein kinase 1-gamma (CK1-gamma), that represses respiration. In humans, CK1-gamma is a critical component of the Wnt signaling pathway, which controls energy metabolism and cell proliferation and is deregulated in many cancers. All together, our data suggest that a single regulatory circuit mediated by the SOD1/CK1-gamma signaling axis links nutrients and reactive oxygen species metabolism to control of energy production.