H2O2/ROS Production, Consumption, and Transport across Organelles

The compartmentalization of cell biochemistry by functionally specialized organelles is the most significant evolutional leap toward diversifying organisms’ capabilities. This transition from prokaryotes to eukaryotes was accompanied by the development of compartmentalized oxygen metabolism. The cost of these oxygen-utilizing reactions is the exposure to macromolecule-damaging oxidation by reactive oxygen species (ROS) by-products. The need for mitigating this hazard was met by evolving elaborate redox-modulating enzymology. The evolutionary process also yielded abilities of higher organisms to utilize the unique properties of oxidants as second messengers. Numerous studies have demonstrated that ROS act as an oxidative agent, causing stress and intracellular signaling mediators. Thus, the oxidation-handling intracellular systems, though robust, are finely tuned to antagonize excess ROS without eliminating them. Although organelles produce ROS primarily as by-products of aerobic metabolism, the endoplasmic reticulum (ER) has the unique property of constantly generating hydrogen peroxide (H₂O₂) during oxidative protein folding.

Further, ER utilizes H₂O₂ to drive the same machinery. The ER’s tolerance to H₂O₂ allows it to act as a significant H₂O₂ source and large-volume ROS reservoir. Thus, ER perturbations can reflect on the global cellular redox and homeostasis. This chapter outlines the mechanisms of ROS/H₂O₂ generation, its control of subcellular distributions, and its contributions to cell activities, with a particular focus on the ER. In this context, it also overviews the cellular factors underlying H₂O₂ transport across the endomembrane, peroxiporins.