Which Antioxidant System Shapes Intracellular HO Gradients?

Cellular antioxidant systems control the levels of hydrogen peroxide (HO) within cells. Multiple theoretical models exist that predict the diffusion properties of HO depending on the rate of HO generation and amount and reaction rates of antioxidant machinery components. Despite these theoretical predictions, it has remained unknown how antioxidant systems shape intracellular HO gradients. The relative role of thioredoxin (Trx) and glutathione systems in HO pattern formation and maintenance is another disputed question. Here, we visualized cellular antioxidant activity and HO gradients formation by exploiting chemogenetic approaches to generate compartmentalized intracellular HO and using the HO biosensor HyPer to analyze the resulting HO distribution in specific subcellular compartments. Using human HeLa cells as a model system, we propose that the Trx system, but not the glutathione system, regulates intracellular HO gradients. 31, 664-670.