(505g) Compartmental Analysis of Redox Metabolism to Inform Therapeutic Strategies

A link between reactive oxygen species (ROS) and malignant tumors has long been noted and suggested as a vulnerability that could be targeted with therapies. However, a lack of quantitative, chemically specific, and mechanistic information has hampered progress. To address this gap, we have combined two approaches. We conducted mathematical analysis of the reaction networks that control hydrogen peroxide (H₂O₂) and nicotinamide adenine dinucleotide phosphate (NADPH) in mitochondria and in the cytosol of human cells. We paired this computational approach with time-dependent measurements of key metabolites and post-translational modifications of important proteins. Insights into how these reaction networks vary from cell type to cell type and as a function of available carbon sources will be shared, concluding with how this new information may be leveraged for therapeutic benefit.