Gnaiger 2023 MitoFit CII: Difference between revisions
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=== Updates to Supplement Figure S1 === | === Updates to Supplement Figure S1 === | ||
Last update 2023-04- | Last update 2023-04-14 | ||
:::: '''Figure S1.''' Complex II ambiguities in graphical representations on FADH<sub>2</sub> as a substrate of Complex II in the canonical forward electron transfer. Chronological sequence of publications from 2001 to 2023. | :::: '''Figure S1.''' Complex II ambiguities in graphical representations on FADH<sub>2</sub> as a substrate of Complex II in the canonical forward electron transfer. Chronological sequence of publications from 2001 to 2023. | ||
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:::::: [[File:El-Gammal 2022 Pflugers Arch CORRECTION.png|400px|link=El-Gammal 2022 Pflugers Arch]] | :::::: [[File:El-Gammal 2022 Pflugers Arch CORRECTION.png|400px|link=El-Gammal 2022 Pflugers Arch]] | ||
:::: '''5''' El-Gammal Z, Nasr MA, Elmehrath AO, Salah RA, Saad SM, El-Badri N (2022) Regulation of mitochondrial temperature in health and disease. '''Pflugers Arch''' 474:1043-51. - [[El-Gammal 2022 Pflugers Arch |»Bioblast link«]] | :::: '''5''' El-Gammal Z, Nasr MA, Elmehrath AO, Salah RA, Saad SM, El-Badri N (2022) Regulation of mitochondrial temperature in health and disease. '''Pflugers Arch''' 474:1043-51. - [[El-Gammal 2022 Pflugers Arch |»Bioblast link«]] | ||
<br> | |||
:::::: [[File:Peng 2022 Front Oncol CORRECTION.png|400px|link=Peng 2022 Front Oncol]] | |||
:::: '''6''' Peng M, Huang Y, Zhang L, Zhao X, Hou Y (2022) Targeting mitochondrial oxidative phosphorylation eradicates acute myeloid leukemic stem cells. '''Front Oncol''' 12:899502. - [[Peng 2022 Front Oncol |»Bioblast link«]] | |||
<br> | <br> | ||
:::::: [[File:Kumar 2021 J Biol Chem CORRECTION.png|400px|link=Kumar 2021 J Biol Chem]] | :::::: [[File:Kumar 2021 J Biol Chem CORRECTION.png|400px|link=Kumar 2021 J Biol Chem]] | ||
:::: ''' | :::: '''7''' Kumar R, Landry AP, Guha A, Vitvitsky V, Lee HJ, Seike K, Reddy P, Lyssiotis CA, Banerjee R (2021) A redox cycle with complex II prioritizes sulfide quinone oxidoreductase dependent H<sub>2</sub>S oxidation. '''J Biol Chem''' 298:101435. - [[Kumar 2021 J Biol Chem |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Hidalgo-Gutierrez CORRECTION.png|400px|link=Hidalgo-Gutierrez 2021 Antioxidants (Basel)]] | :::::: [[File:Hidalgo-Gutierrez CORRECTION.png|400px|link=Hidalgo-Gutierrez 2021 Antioxidants (Basel)]] | ||
:::: ''' | :::: '''8''' Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, Barriocanal-Casado E, López-Herrador S, Quinzii CM, López LC (2021) Metabolic targets of coenzyme Q10 in mitochondria. '''Antioxidants (Basel)''' 10:520. - [[Hidalgo-Gutierrez 2021 Antioxidants (Basel) |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Han 2021 Am J Respir Cell Mol Biol CORRECTION.png|400px|link=Han 2021 Am J Respir Cell Mol Biol]] | :::::: [[File:Han 2021 Am J Respir Cell Mol Biol CORRECTION.png|400px|link=Han 2021 Am J Respir Cell Mol Biol]] | ||
:::: ''' | :::: '''9''' Han S, Chandel NS (2021) Lessons from cancer metabolism for pulmonary arterial hypertension and fibrosis. '''Am J Respir Cell Mol Biol''' 65:134-45. - [[Han 2021 Am J Respir Cell Mol Biol |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Chakrabarty 2021 Cell Stem Cell 1 CORRECTION.png|400px|link=Chakrabarty 2021 Cell Stem Cell]] | :::::: [[File:Chakrabarty 2021 Cell Stem Cell 1 CORRECTION.png|400px|link=Chakrabarty 2021 Cell Stem Cell]] | ||
:::::: [[File:Chakrabarty 2021 Cell Stem Cell 3 CORRECTION.png|400px|link=Chakrabarty 2021 Cell Stem Cell]] | :::::: [[File:Chakrabarty 2021 Cell Stem Cell 3 CORRECTION.png|400px|link=Chakrabarty 2021 Cell Stem Cell]] | ||
:::: ''' | :::: '''10''' Chakrabarty RP, Chandel NS (2021) Mitochondria as signaling organelles control mammalian stem cell fate. '''Cell Stem Cell''' 28:394-408. - [[Chakrabarty 2021 Cell Stem Cell |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Martinez-Reyes 2020 Nature CORRECTION.png|400px|link=Martinez-Reyes 2020 Nature]] | :::::: [[File:Martinez-Reyes 2020 Nature CORRECTION.png|400px|link=Martinez-Reyes 2020 Nature]] | ||
:::: ''' | :::: '''11''' Martínez-Reyes I, Cardona LR, Kong H, Vasan K, McElroy GS, Werner M, Kihshen H, Reczek CR, Weinberg SE, Gao P, Steinert EM, Piseaux R, Budinger GRS, Chandel NS (2020) Mitochondrial ubiquinol oxidation is necessary for tumour growth. '''Nature''' 585:288-92. - [[Martinez-Reyes 2020 Nature |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:McElroy 2020 Cell Metab CORRECTION.png|400px|link=McElroy 2020 Cell Metab]] | :::::: [[File:McElroy 2020 Cell Metab CORRECTION.png|400px|link=McElroy 2020 Cell Metab]] | ||
:::: ''' | :::: '''12''' McElroy GS, Reczek CR, Reyfman PA, Mithal DS, Horbinski CM, Chandel NS (2020) NAD+ regeneration rescues lifespan, but not ataxia, in a mouse model of brain mitochondrial Complex I dysfunction. '''Cell Metab''' 32:301-8.e6. - [[McElroy 2020 Cell Metab |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Jian 2020 Cell Metab CORRECTION.png|400px|link=Jian 2020 Cell Metab]] | :::::: [[File:Jian 2020 Cell Metab CORRECTION.png|400px|link=Jian 2020 Cell Metab]] | ||
:::: ''' | :::: '''13''' Jian C, Fu J, Cheng X, Shen LJ, Ji YX, Wang X, Pan S, Tian H, Tian S, Liao R, Song K, Wang HP, Zhang X, Wang Y, Huang Z, She ZG, Zhang XJ, Zhu L, Li H (2020) Low-dose sorafenib acts as a mitochondrial uncoupler and ameliorates nonalcoholic steatohepatitis. '''Cell Metab''' 31:892-908. - [[Jian 2020 Cell Metab |»Bioblast link«]] | ||
:::::: While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH<sub>2</sub> as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate. | :::::: While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH<sub>2</sub> as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate. | ||
<br> | <br> | ||
:::::: [[File:Szabo 2020 Int J Mol Sci CORRECTION.png|400px|link=Szabo 2020 Int J Mol Sci]] | :::::: [[File:Szabo 2020 Int J Mol Sci CORRECTION.png|400px|link=Szabo 2020 Int J Mol Sci]] | ||
:::: ''' | :::: '''14''' Szabo L, Eckert A, Grimm A (2020) Insights into disease-associated tau impact on mitochondria. '''Int J Mol Sci''' 21:6344. - [[Szabo 2020 Int J Mol Sci |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Tabassum 2020 J Biomed Res Environ Sci CORRECTION.png|400px|link=Tabassum 2020 J Biomed Res Environ Sci]] | :::::: [[File:Tabassum 2020 J Biomed Res Environ Sci CORRECTION.png|400px|link=Tabassum 2020 J Biomed Res Environ Sci]] | ||
:::: ''' | :::: '''15''' Tabassum N, Kheya IS, Ibn Asaduzzaman SA, Maniha SM, Fayz AH, Zakaria A, Fayz AH, Zakaria A, Noor R (2020) A review on the possible leakage of electrons through the electron transport chain within mitochondria. '''J Biomed Res Environ Sci''' 1:105-13. - [[Tabassum 2020 J Biomed Res Environ Sci |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Yang 2020 Transl Neurodegener CORRECTION.png|400px|link=Yang 2020 Transl Neurodegener]] | :::::: [[File:Yang 2020 Transl Neurodegener CORRECTION.png|400px|link=Yang 2020 Transl Neurodegener]] | ||
:::: ''' | :::: '''16''' Yang L, Youngblood H, Wu C, Zhang Q (2020) Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation. '''Transl Neurodegener''' 9:19. - [[Yang 2020 Transl Neurodegener |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Vekshin 2020 Springer Cham CORRECTION.png|400px|link=Vekshin 2020 Springer Cham]] | :::::: [[File:Vekshin 2020 Springer Cham CORRECTION.png|400px|link=Vekshin 2020 Springer Cham]] | ||
:::: ''' | :::: '''17''' Vekshin N (2020) Biophysics of mitochondria. '''Springer Cham''': 197 pp. - [[Vekshin 2020 Springer Cham |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Han 2019 Am J Respir Cell Mol Biol CORRECTION.png|400px|link=Han 2019 Am J Respir Cell Mol Biol]] | :::::: [[File:Han 2019 Am J Respir Cell Mol Biol CORRECTION.png|400px|link=Han 2019 Am J Respir Cell Mol Biol]] | ||
:::: ''' | :::: '''18''' Han S, Chandel NS (2019) There is no smoke without mitochondria. '''Am J Respir Cell Mol Biol''' 60:489-91. - [[Han 2019 Am J Respir Cell Mol Biol |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Grandoch 2019 Nat Metab CORRECTION.png|300px|link=Grandoch 2019 Nat Metab]] | :::::: [[File:Grandoch 2019 Nat Metab CORRECTION.png|300px|link=Grandoch 2019 Nat Metab]] | ||
:::: ''' | :::: '''19''' Grandoch M, Flögel U, Virtue S, Maier JK, Jelenik T, Kohlmorgen C, Feldmann K, Ostendorf Y, Castañeda TR, Zhou Z, Yamaguchi Y, Nascimento EBM, Sunkari VG, Goy C, Kinzig M, Sörgel F, Bollyky PL, Schrauwen P, Al-Hasani H, Roden M, Keipert S, Vidal-Puig A, Jastroch M5, Haendeler J, Fischer JW (2019) 4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue. '''Nat Metab''' 1:546-59. - [[Grandoch 2019 Nat Metab |»Bioblast link«]] | ||
:::::: '''NADH''' is shown as the '''''product''''' of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequenty encountered when '''FADH<sub>2</sub>''' is shown as the '''''substrate''''' of CII. | :::::: '''NADH''' is shown as the '''''product''''' of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequenty encountered when '''FADH<sub>2</sub>''' is shown as the '''''substrate''''' of CII. | ||
<br> | <br> | ||
:::::: [[File:McCollum 2019 Front Plant Sci CORRECTION.png|400px|link=McCollum 2019 Front Plant Sci]] | :::::: [[File:McCollum 2019 Front Plant Sci CORRECTION.png|400px|link=McCollum 2019 Front Plant Sci]] | ||
:::: ''' | :::: '''20''' McCollum C, Geißelsöder S, Engelsdorf T, Voitsik AM, Voll LM (2019) Deficiencies in the mitochondrial electron transport chain affect redox poise and resistance toward Colletotrichum higginsianum. '''Front Plant Sci''' 10:1262. - [[McCollum 2019 Front Plant Sci |»Bioblast link«]] | ||
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:::::: [[File:Cronshaw 2019 Photobiomodul Photomed Laser Surg CORRECTION.png|400px|link=Cronshaw 2019 Photobiomodul Photomed Laser Surg]] | :::::: [[File:Cronshaw 2019 Photobiomodul Photomed Laser Surg CORRECTION.png|400px|link=Cronshaw 2019 Photobiomodul Photomed Laser Surg]] | ||
:::: ''' | :::: '''21''' Cronshaw M, Parker S, Arany P (2019) Feeling the heat: evolutionary and microbial basis for the analgesic mechanisms of photobiomodulation therapy. '''Photobiomodul Photomed Laser Surg''' 37:517-26. - [[Cronshaw 2019 Photobiomodul Photomed Laser Surg |»Bioblast link«]] | ||
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:::::: [[File:Torres 2017 Cell Metab CORRECTION.png|400px|link=Torres 2017 Cell Metab]] | :::::: [[File:Torres 2017 Cell Metab CORRECTION.png|400px|link=Torres 2017 Cell Metab]] | ||
:::: ''' | :::: '''22''' Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, Neufer PD (2017) 17β-estradiol directly lowers mitochondrial membrane microviscosity and improves bioenergetic function in skeletal muscle. '''Cell Metab''' 27:167-79. - [[Torres 2017 Cell Metab |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:McElroy 2017 Exp Cell Res.png|400px|link=McElroy 2017 Exp Cell Res]] | :::::: [[File:McElroy 2017 Exp Cell Res.png|400px|link=McElroy 2017 Exp Cell Res]] | ||
:::: ''' | :::: '''23''' McElroy GS, Chandel NS (2017) Mitochondria control acute and chronic responses to hypoxia. '''Exp Cell Res''' 356:217-22. - [[McElroy 2017 Exp Cell Res |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Martinez-Reyes 2016 Mol Cell CORRECTION.png|400px|link=Martinez-Reyes 2016 Mol Cell]] | :::::: [[File:Martinez-Reyes 2016 Mol Cell CORRECTION.png|400px|link=Martinez-Reyes 2016 Mol Cell]] | ||
:::: ''' | :::: '''24''' Martínez-Reyes I, Diebold LP, Kong H, Schieber M, Huang H, Hensley CT, Mehta MM, Wang T, Santos JH, Woychik R, Dufour E, Spelbrink JN, Weinberg SE, Zhao Y, DeBerardinis RJ, Chandel NS (2016) TCA cycle and mitochondrial membrane potential are necessary for diverse biological functions. '''Mol Cell''' 61:199-209. - [[Martinez-Reyes 2016 Mol Cell |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Cadonic 2016 Mol Neurobiol CORRECTION.png|400px|link=Cadonic 2016 Mol Neurobiol]] | :::::: [[File:Cadonic 2016 Mol Neurobiol CORRECTION.png|400px|link=Cadonic 2016 Mol Neurobiol]] | ||
:::: ''' | :::: '''25''' Cadonic C, Sabbir MG, Albensi BC (2016) Mechanisms of mitochondrial dysfunction in Alzheimer's disease. '''Mol Neurobiol''' 53:6078-90. - [[Cadonic 2016 Mol Neurobiol |»Bioblast link«]] | ||
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:::::: [[File:Sullivan 2014 Cell Cycle CORRECTION.png|400px|link=Sullivan 2014 Cell Cycle]] | :::::: [[File:Sullivan 2014 Cell Cycle CORRECTION.png|400px|link=Sullivan 2014 Cell Cycle]] | ||
:::: ''' | :::: '''26''' Sullivan LB, Chandel NS. (2014) Mitochondrial metabolism in TCA cycle mutant cancer cells. '''Cell Cycle''' 13:347-8. - [[Sullivan 2014 Cell Cycle |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Beutner 2014 PLoS One CORRECTION.png|400px|link=Beutner 2014 PLoS One]] | :::::: [[File:Beutner 2014 PLoS One CORRECTION.png|400px|link=Beutner 2014 PLoS One]] | ||
:::: ''' | :::: '''27''' Beutner G, Eliseev RA, Porter GA Jr (2014) Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes. '''PLoS One''' 9:e113330. - [[Beutner 2014 PLoS One |»Bioblast link«]] | ||
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:::::: [[File:Hamanaka 2013 Cell Logist CORRECTION.png|400px|link=Hamanaka 2013 Cell Logist]] | :::::: [[File:Hamanaka 2013 Cell Logist CORRECTION.png|400px|link=Hamanaka 2013 Cell Logist]] | ||
:::: ''' | :::: '''28''' Hamanaka RB, Chandel NS (2013) Mitochondrial metabolism as a regulator of keratinocyte differentiation. '''Cell Logist''' 3:e25456. - [[Hamanaka 2013 Cell Logist |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Johnson 2013 Eukaryot Cell CORRECTION.png|400px|link=Johnson 2013 Eukaryot Cell]] | :::::: [[File:Johnson 2013 Eukaryot Cell CORRECTION.png|400px|link=Johnson 2013 Eukaryot Cell]] | ||
:::: ''' | :::: '''29''' Johnson X, Alric J (2013) Central carbon metabolism and electron transport in Chlamydomonas reinhardtii: metabolic constraints for carbon partitioning between oil and starch. '''Eukaryot Cell''' 12:776-93. - [[Johnson 2013 Eukaryot Cell |»Bioblast link«]] | ||
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:::::: [[File:Keane 2011 Parkinsons Dis CORRECTION.png|400px|link=Keane 2011 Parkinsons Dis]] | :::::: [[File:Keane 2011 Parkinsons Dis CORRECTION.png|400px|link=Keane 2011 Parkinsons Dis]] | ||
:::: ''' | :::: '''30''' Keane PC, Kurzawa M, Blain PG, Morris CM (2011) Mitochondrial dysfunction in Parkinson's disease. '''Parkinsons Dis''' 2011:716871. - [[Keane 2011 Parkinsons Dis |»Bioblast link«]] | ||
<br> | <br> | ||
:::::: [[File:Snyder 2009 Antioxid Redox Signal.png|400px|link=Snyder 2009 Antioxid Redox Signal]] | :::::: [[File:Snyder 2009 Antioxid Redox Signal.png|400px|link=Snyder 2009 Antioxid Redox Signal]] | ||
:::: ''' | :::: '''31''' Hamanaka RB, Chandel NS (2013) Snyder CM, Chandel NS (2009) Mitochondrial regulation of cell survival and death during low-oxygen conditions. '''Antioxid Redox Signal''' 11:2673-83. - [[Snyder 2009 Antioxid Redox Signal |»Bioblast link«]] | ||
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:::::: [[File:Liu 2009 J Biomed Sci CORRECTION.png|400px|link=Liu 2009 J Biomed Sci]] | :::::: [[File:Liu 2009 J Biomed Sci CORRECTION.png|400px|link=Liu 2009 J Biomed Sci]] | ||
:::: ''' | :::: '''32''' Liu Y, Schubert DR (2009) The specificity of neuroprotection by antioxidants. '''J Biomed Sci''' 16:98. - [[Liu 2009 J Biomed Sci |»Bioblast link«]] | ||
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:::::: [[File:Balaban 2005 Cell CORRECTION.png|400px|link=Balaban 2005 Cell]] | :::::: [[File:Balaban 2005 Cell CORRECTION.png|400px|link=Balaban 2005 Cell]] | ||
:::: ''' | :::: '''33''' Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. '''Cell''' 120:483-95. - [[Balaban 2005 Cell |»Bioblast link«]] | ||
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:::::: [[File:Brownlee 2003 J Clin Invest CORRECTION.png|400px|link=Brownlee 2003 J Clin Invest]] | :::::: [[File:Brownlee 2003 J Clin Invest CORRECTION.png|400px|link=Brownlee 2003 J Clin Invest]] | ||
:::: ''' | :::: '''34''' Brownlee M (2003) A radical explanation for glucose-induced beta cell dysfunction. '''J Clin Invest''' 112:1788-90. - [[Brownlee 2003 J Clin Invest |»Bioblast link«]] | ||
<br> | <br> | ||
Revision as of 06:47, 14 April 2023
Gnaiger E (2023) Complex II ambiguities ― FADH2 in the electron transfer system. MitoFit Preprints 2023.3.v2. https://doi.org/10.26124/mitofit:2023-0003.v2 |
» MitoFit Preprints 2023.3.v2.
Complex II ambiguities ― FADH2 in the electron transfer system
Gnaiger Erich (2023) MitoFit Prep
Abstract:
- Version 2 (v2) 2023-04-04 10.26124/mitofit:2023-0003.v2
- Version 1 (v1) 2023-03-247 10.26124/mitofit:2023-0003 - »Link to all versions«
The current narrative that the reduced coenzymes NADH and FADH2 feed electrons from the tricarboxylic acid cycle into the mitochondrial electron transfer system creates ambiguities around respiratory Complex II (CII). The succinate dehydrogenase subunit SDHA of CII oxidizes succinate and reduces covalently bound FAD to FADH2 in the canonical forward tricarboxylic acid cycle. However, several graphical representations of the membrane-bound electron transfer system (ETS) depict FADH2 in the mitochondrial matrix to be oxidized by CII. This leads to the false conclusion that FADH2 feeds electrons into the ETS through CII, including FADH2 from the tricarboxylic acid cycle, the β-oxidation cycle in fatty acid oxidation, and the glycerophosphate shuttle. In reality, FAD and succinate are the substrates of SDHA at the ETS-entry into CII. The reduced flavin groups FADH2 and FMNH2 are products downstream within CII and CI, respectively. Further electron transfer converges at the coenzyme Q-junction. Similarly, electron transferring flavoprotein and mitochondrial glycerophosphate dehydrogenase feed electrons into the Q-junction but not through CII. The ambiguities surrounding Complex II in the literature and educational tools call for quality control, to secure scientific standards in current communications on bioenergetics and ultimately support adequate clinical applications.
• Keywords: coenzyme Q junction; Complex CII; electron transfer system; fatty acid oxidation; flavin adenine dinucleotide;
succinate dehydrogenase; tricarboxylic acid cycle
• O2k-Network Lab: AT Innsbruck Oroboros
- Figure 1. Complex II bridges electron transfer from the TCA cycle to the mitochondrial inner membrane. Graphical representations of the electron transfer system ETS with successive emphasis on pathway architecture and concomitant loss of detail. CII is integrated in the TCA cycle (matrix-ETS) and the membrane-bound electron transfer system (membrane-ETS in the mt-inner membrane mtIM). Joint half-circular arrows indicate electron transfer 2{H++e-}, distinguished from hydrogen ion H+ transport across the mtIM. (a) In the soluble domain of CII, the flavoprotein SDHA catalyzes the oxidation succinate → fumarate+2{H++e-} and reduction FAD+2{H++e-} → FADH2. The iron–sulfur protein SDHB transfers electrons through Fe-S clusters to the mtIM domain where ubiquinone UQ is reduced with 2{H++e-} to ubiquinol UQH2 in SDHC and SDHD. (b) NADH and succinate are substrates of redox reactions in CI and CII, respectively, with FMNH2 and FADH2 as the corresponding products. Succinate and fumarate indicate the chemical entities irrespective of ionization, whereas the charges are shown in NADH, NAD+, and H+. (c) Electron flow catalyzed by dehydrognases localized in the mitochondrial (mt) matrix converges at the N-junction, reducing NAD+ to NADH. Electron flow from NADH and succinate S to molecular oxygen, 2{H++e-}+0.5 O2 ⇢ H2O, converges through CI and CII at the Q-junction. CIII passes electrons to cytochrome c and in CIV to O2.
ORCID: Gnaiger Erich, Oroboros Instruments, Innsbruck, Austria
- Acknowledgements: I thank Luiza H. Cardoso and Sabine Schmitt for stimulating discussions, and Paolo Cocco for expert help on the graphical abstract and Figures 1b and c. Contribution to the European Union’s Horizon 2020 research and innovation program Grant 857394 (FAT4BRAIN).
Updates to Supplement Figure S1
Last update 2023-04-14
- Figure S1. Complex II ambiguities in graphical representations on FADH2 as a substrate of Complex II in the canonical forward electron transfer. Chronological sequence of publications from 2001 to 2023.
- 1 Shirakawa R, Nakajima T, Yoshimura A, Kawahara Y, Orito C, Yamane M, Handa H, Takada S, Furihata T, Fukushima A, Ishimori N, Nakagawa M, Yokota I, Sabe H, Hashino S, Kinugawa S, Yokota T (2023) Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults. Sci Rep 13:5203. - »Bioblast link«
- While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH2 as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate.
- 2 Eyenga P, Rey B, Eyenga L, Sheu SS (2022) Regulation of oxidative phosphorylation of liver mitochondria in sepsis. Cells 11:1598. - »Bioblast link«
- 3 Tseng W-W, Wei A-C (2022) Kinetic mathematical modeling of oxidative phosphorylation in cardiomyocyte mitochondria. Cells 11:4020. - »Bioblast link«
- 4 Bețiu AM, Noveanu L, Hâncu IM, Lascu A, Petrescu L, Maack C, Elmér E, Muntean DM (2022) Mitochondrial effects of common cardiovascular medications: the good, the bad and the mixed. Int J Mol Sci 23:13653. - »Bioblast link«
- 5 El-Gammal Z, Nasr MA, Elmehrath AO, Salah RA, Saad SM, El-Badri N (2022) Regulation of mitochondrial temperature in health and disease. Pflugers Arch 474:1043-51. - »Bioblast link«
- 6 Peng M, Huang Y, Zhang L, Zhao X, Hou Y (2022) Targeting mitochondrial oxidative phosphorylation eradicates acute myeloid leukemic stem cells. Front Oncol 12:899502. - »Bioblast link«
- 7 Kumar R, Landry AP, Guha A, Vitvitsky V, Lee HJ, Seike K, Reddy P, Lyssiotis CA, Banerjee R (2021) A redox cycle with complex II prioritizes sulfide quinone oxidoreductase dependent H2S oxidation. J Biol Chem 298:101435. - »Bioblast link«
- 8 Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, Barriocanal-Casado E, López-Herrador S, Quinzii CM, López LC (2021) Metabolic targets of coenzyme Q10 in mitochondria. Antioxidants (Basel) 10:520. - »Bioblast link«
- 9 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«
- 10 Chakrabarty RP, Chandel NS (2021) Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell 28:394-408. - »Bioblast link«
- 11 Martínez-Reyes I, Cardona LR, Kong H, Vasan K, McElroy GS, Werner M, Kihshen H, Reczek CR, Weinberg SE, Gao P, Steinert EM, Piseaux R, Budinger GRS, Chandel NS (2020) Mitochondrial ubiquinol oxidation is necessary for tumour growth. Nature 585:288-92. - »Bioblast link«
- 12 McElroy GS, Reczek CR, Reyfman PA, Mithal DS, Horbinski CM, Chandel NS (2020) NAD+ regeneration rescues lifespan, but not ataxia, in a mouse model of brain mitochondrial Complex I dysfunction. Cell Metab 32:301-8.e6. - »Bioblast link«
- 13 Jian C, Fu J, Cheng X, Shen LJ, Ji YX, Wang X, Pan S, Tian H, Tian S, Liao R, Song K, Wang HP, Zhang X, Wang Y, Huang Z, She ZG, Zhang XJ, Zhu L, Li H (2020) Low-dose sorafenib acts as a mitochondrial uncoupler and ameliorates nonalcoholic steatohepatitis. Cell Metab 31:892-908. - »Bioblast link«
- While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH2 as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate.
- 14 Szabo L, Eckert A, Grimm A (2020) Insights into disease-associated tau impact on mitochondria. Int J Mol Sci 21:6344. - »Bioblast link«
- 15 Tabassum N, Kheya IS, Ibn Asaduzzaman SA, Maniha SM, Fayz AH, Zakaria A, Fayz AH, Zakaria A, Noor R (2020) A review on the possible leakage of electrons through the electron transport chain within mitochondria. J Biomed Res Environ Sci 1:105-13. - »Bioblast link«
- 16 Yang L, Youngblood H, Wu C, Zhang Q (2020) Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation. Transl Neurodegener 9:19. - »Bioblast link«
- 17 Vekshin N (2020) Biophysics of mitochondria. Springer Cham: 197 pp. - »Bioblast link«
- 18 Han S, Chandel NS (2019) There is no smoke without mitochondria. Am J Respir Cell Mol Biol 60:489-91. - »Bioblast link«
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- NADH is shown as the product of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequenty encountered when FADH2 is shown as the substrate of CII.
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Supplement Figure S1 (v2)
- Figure S1. Complex II ambiguities in graphical representations on FADH2 as a substrate of Complex II in the canonical forward electron transfer. Chronological sequence of publications from 2001 to 2023.
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Supplement Figure S2 (v2)
- Figure S2. Complex II ambiguities in graphical representations on FADH2 as a substrate of Complex II in the canonical forward electron transfer (retrieved 2023-03-21 to 2023-04-04)
- Website 1: OpenStax Biology - Fig. 7.10 Oxidative phosphorylation (CC BY 3.0). - OpenStax Biology got it wrong in figures and text. The error is copied without quality assessment and propagated in several links.
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