Complex II ambiguities

high-resolution terminology - matching measurements at high-resolution

Complex II ambiguities

Description

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 (2024) Complex II ambiguities ― FADH₂ in the electron transfer system. J Biol Chem 300: 105470. https://doi.org/10.1016/j.jbc.2023.105470

» Links: Ambiguity crisis, Complex I and hydrogen ion ambiguities in the electron transfer system

A game of cards

33 copies or variations of a CII ambiguity theme

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12. Vesga LC, Silva AMP, Bernal CC, Mendez-Sánchez SC, Bohórquez ARR (2021) Tetrahydroquinoline/4,5-dihydroisoxazole hybrids with a remarkable effect over mitochondrial bioenergetic metabolism on melanoma cell line B16F10. Med Chem Res 30:2127–43. - »Bioblast link«

13. Gopalakrishnan S, Mehrvar S, Maleki S, Schmitt H, Summerfelt P, Dubis AM, Abroe B, Connor TB Jr, Carroll J, Huddleston W, Ranji M, Eells JT (2020) Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa. Sci Rep 10:20382. - »Bioblast link«

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15. Lu F (2023) Hypothetical hydrogenase activity of human mitochondrial Complex I and its role in preventing cancer transformation. Explor Res Hypothesis Med 8:280-5. - »Bioblast link«

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17. Faria R, Boisguérin P, Sousa Â, Costa D (2023) Delivery systems for mitochondrial gene therapy: a review. Pharmaceutics 15:572. - »Bioblast link«

18. George CE, Saunders CV, Morrison A, Scorer T, Jones S, Dempsey NC (2023) Cold stored platelets in the management of bleeding: is it about bioenergetics? Platelets 34:2188969 - »Bioblast link«

19. Narine M, Colognato H (2022) Current insights into oligodendrocyte metabolism and its power to sculpt the myelin landscape. Front Cell Neurosci 16:892968. - »Bioblast link«

20. Sainero-Alcolado L, Liaño-Pons J, Ruiz-Pérez MV, Arsenian-Henriksson M (2022) Targeting mitochondrial metabolism for precision medicine in cancer. Cell Death Differ 29:1304-17. - »Bioblast link«

21. Nguyen TT, Nguyen DK, Ou YY (2021) Addressing data imbalance problems in ligand-binding site prediction using a variational autoencoder and a convolutional neural network. Brief Bioinform 22:bbab277. - »Bioblast link«

22. Prasuhn J, Davis RL, Kumar KR (2021) Targeting mitochondrial impairment in Parkinson's disease: challenges and opportunities. Front Cell Dev Biol 8:615461. - »Bioblast link«

23. Gallinat A, Vilahur G, Padró T, Badimon L (2022) Network-assisted systems biology analysis of the mitochondrial proteome in a pre-clinical model of ischemia, revascularization and post-conditioning. Int J Mol Sci 23:2087. - »Bioblast link«

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25. Keidar N, Peretz NK, Yaniv Y (2023) Ca²⁺ pushes and pulls energetics to maintain ATP balance in atrial cells: computational insights. Front Physiol 14:1231259. - »Bioblast link«

26. Chakrabarty RP, Chandel NS (2021) Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell 28:394-408. - »Bioblast link«

27. Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, Madrigal-Santillán EO, Morales-Martínez M, Madrigal-Bujaidar E, Álvarez-González I, Gutiérrez-Salinas J, Esquivel-Chirino C, Chamorro-Cevallos G, Cristóbal-Luna JM, Morales-González JA (2021) Oxidative stress, mitochondrial function and adaptation to exercise: new perspectives in nutrition. Life (Basel) 11:1269. - »Bioblast link«

28. Egan B, Sharples AP (2023) Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training. Physiol Rev 103:2057-2170. - »Bioblast link«

29. Han S, Chandel NS (2021) Lessons from cancer metabolism for pulmonary arterial hypertension and fibrosis. Am J Respir Cell Mol Biol 65:134-45. - »Bioblast link«

30. Iakovou E, Kourti M (2022) A comprehensive overview of the complex role of oxidative stress in aging, the contributing environmental stressors and emerging antioxidant therapeutic interventions. Front Aging Neurosci 14:827900. - »Bioblast link«

31. Jayasankar V, Vrdoljak N, Roma A, Ahmed N, Tcheng M, Minden MD, Spagnuolo PA (2022) Novel mango ginger bioactive (2,4,6-trihydroxy-3,5-diprenyldihydrochalcone) inhibits mitochondrial metabolism in combination with Avocatin B. ACS Omega 7:1682-93. - »Bioblast link«

32. Yuan Q, Zeng ZL, Yang S, Li A, Zu X, Liu J (2022) Mitochondrial stress in metabolic inflammation: modest benefits and full losses. Oxid Med Cell Longev 2022:8803404. - »Bioblast link«

33. Yin M, O'Neill LAJ (2021) The role of the electron transport chain in immunity. FASEB J 35:e21974. - »Bioblast link«

Doubles

1. Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. Circ Res 114:524-37. - »Bioblast link«

2. Chen CL, Zhang L, Jin Z, Kasumov T, Chen YR (2022) Mitochondrial redox regulation and myocardial ischemia-reperfusion injury. Am J Physiol Cell Physiol 322:C12-23. - »Bioblast link«

1. Chen TH, Koh KY, Lin KM, Chou CK (2022) Mitochondrial dysfunction as an underlying cause of skeletal muscle disorders. Int J Mol Sci 23:12926. - »Bioblast link«

2. Schniertshauer D, Wespel S, Bergemann J (2023) Natural mitochondria targeting substances and their effect on cellular antioxidant system as a potential benefit in mitochondrial medicine for prevention and remediation of mitochondrial dysfunctions. Curr Issues Mol Biol 45:3911-32. - »Bioblast link«

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