Abstract

Overview

Oxidative modifications are known disruptors of protein structure and function, contributing to aging and disease. Traditional oxidation involves the dispersal of reactive oxygen species (ROS) that attack protein surfaces.

Findings

We introduce a new pathway called O2-confined photooxidation wherein oxygen is trapped within protein folds, leading to damage. This unique process involves capturing O2 in protein cavities, and its transformation into multiple ROS forms, mostly facilitated by tryptophan residues when exposed to blue light. This ROS then specifically damages the interior of proteins through a mechanism of constrained diffusion.

Evidence from whole-cell proteomic analysis indicates that this photooxidative reaction extensively affects various cellular proteins. This mechanism is particularly relevant to human tissues directly exposed to visible light, such as skin and eyes.

Conclusion

This study unveils a potentially hidden oxidative pathway in proteins subjected to visible light, suggesting a broader impact on cellular health and aging.