Alyson Colin

Alyson
Colin

Cu/Zn Superoxide Dismutase (SOD1) is an abundant protein and highly conserved across the eukaryotic domain. Surprisingly, only a minimal amount of SOD1 is required to prevent intracellular oxidative stress, which begs the question: What is the purpose for its large excess? We propose that a major role of SOD1 in cell biology is to mediate redox-signaling cascades through its ability to disproportionate superoxide into oxygen and hydrogen peroxide, the latter of which is a well-known redox signal. Recent studies show that the peroxide generated by SOD1 is able to stabilize a membrane-tethered yeast casein kinase (YCK1). This stabilization leads to a metabolic switch from respiration to fermentation, which is the favored mode of metabolism for cancerous cells. Our results between SOD1 and casein kinase were observed in mammalian cell lines as well, but the mechanistic details are unknown for both cells types. Therefore, this research has the potential to further our current knowledge of cancer cell metabolism. Through a proteomics approach and a genetic screen, we will elucidate the mechanism of YCK1-SOD1 stabilization in yeast, while studying the homologous, mammalian Wnt signaling pathway in parallel. We anticipate our studies will uncover new and exciting aspects of the redox biology of SOD1 that go well beyond its role in oxidative stress protection.

Reddi
School of Chemistry and Biochemistry