Mitochondrial redox flux and signaling. A. Nutrient catabolism and the liberation of electrons is coupled to the formation of NADH and NADPH which are utilized to support pro-oxidant and antioxidant activities in mitochondria. This results in spatiotemporal changes in mitochondrial redox buffering networks conveying signals that regulate protein function through cysteine switches. B. 10 potential sites for H2O2 production by mitochondria (represented by red star). Note the topology of H2O2 formation relative to the mitochondrial inner membrane. Sites include Complex I, Complex II (succinate dehydrogenase; Sdh), Complex III, 2-oxoglutarate dehydrogenase (Odh), pyruvate dehydrogenase (Pdh), branched-chain keto acid dehydrogenase (Bckdh), electron-transferring flavoprotein-ubiquinone oxidoreductase (Etfqo), sn-glycerol-3-phosphate dehydrogenase (G3PDH), dihydroorotate dehydrogenase (Dhodh), and sulfide quinone oxidoreductase (Sqr). FMN-Complex I; IF, quinone binding site Complex I; IQ, FAD-Complex II; IIF, quinone binding site Complex II; IIQ, quinone binding site outer leaflet Complex III; IIIQo, quinone binding site inner leaflet Complex III; IIIQi, 2-oxoglutarate; 2-OG, branched chain amino acid; Bcaa, dihydroorotate; Dho. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)