Fig. 5.

(Top) Schematic of the aerobic respiratory electron transport chain in E. coli. Red arrows depict flow of electrons; black arrows depict chemical reactions. The NDH complex transfers electrons from NADH to ubiquinone (UQ) to form UQH₂. UQH₂ carries electrons to the terminal cytochrome oxidase-bo₃, which converts O₂ to H₂O in a four-electron reduction process. Helices depict CM15, which permeabilizes the cytoplasmic membrane seconds before the onset of oxidative stress. We suggest that CM15 induces premature release of O₂^– from cytochrome oxidase-bo₃. The data argue against a mechanism of enhanced autoxidation of the reduced flavin cofactor within NDH or of UQH₂. (Bottom) A burst of O₂^– enhances free Fe²⁺ by attacking Fe-containing enzymes and enhances H₂O₂ by the action of superoxide dismutase. This leads to cycling of the Fenton reaction, resulting in enhanced autofluorescence from oxidized flavin species (FAD) and further oxidation of CellROX Green.