The current narrative that the reduced coenzymes NADH and FADH2 feed electrons from the tricarboxylic acid (TCA) cycle into the mitochondrial electron transfer system can create ambiguities around respiratory Complex CII. Succinate dehydrogenase or CII reduces FAD to FADH2 in the canonical forward TCA cycle. However, some graphical representations of the membrane-bound electron transfer system (ETS) depict CII as the site of oxidation of FADH2. This leads to the false believe that FADH2 generated by electron transferring flavoprotein (CETF) in fatty acid oxidation and mitochondrial glycerophosphate dehydrogenase (CGpDH) feeds electrons into the ETS through CII. In reality, NADH and succinate produced in the TCA cycle are the substrates of Complexes CI and CII, respectively, and the reduced flavin groups FMNH2 and FADH2 are downstream products of CI and CII, respectively, carrying electrons from CI and CII into the Q-junction. Similarly, CETF and CGpDH feed electrons into the Q-junction but not through CII. The ambiguities surrounding Complex II in the literature call for quality control, to secure scientific standards in current communications on bioenergetics and support adequate clinical applications.
Abbreviation: CII ambiguities
Reference: Gnaiger E (2023) Complex II ambiguities ― FADH2 in the electron transfer system. MitoFit Preprints 2023.3. https://doi.org/10.26124/mitofit:2023-0003
MitoPedia concepts: MiP concept
MitoPedia topics: Enzyme, Substrate and metabolite