Gnaiger 2023 MitoFit CII: Difference between revisions

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{{Publication
{{Publication
|title=Gnaiger E (2023) Complex II ambiguities ā€• FADH<sub>2</sub> in the electron transfer system. MitoFit Preprints 2023.3. https://doi.org/10.26124/mitofit:2023-0003
|title=Gnaiger E (2023) Complex II ambiguities ā€• FADH<sub>2</sub> in the electron transfer system. MitoFit Preprints 2023.3.v6. https://doi.org/10.26124/mitofit:2023-0003.v6 - ''' [[Gnaiger 2024 J Biol Chem |''Published 2023-11-22 J Biol Chem (2024)'']]
|info=MitoFit Preprints 2023.3. [[File:MitoFit Preprints pdf.png|left|160px|link=https://wiki.oroboros.at/images/a/ae/Gnaiger_2023_MitoFit_CII.pdf|MitoFit pdf]] [https://wiki.oroboros.at/images/a/ae/Gnaiger_2023_MitoFit_CII.pdf Complex II ambiguities ā€• FADH<sub>2</sub> in the electron transfer system]<br/>
|info=MitoFit Preprints 2023.3.v6. [[File:MitoFit Preprints pdf.png|left|160px|link=https://wiki.oroboros.at/images/a/ae/Gnaiger_2023_MitoFit_CII.pdf|MitoFit pdf]] [https://wiki.oroboros.at/images/a/ae/Gnaiger_2023_MitoFit_CII.pdf Complex II ambiguities ā€• FADH<sub>2</sub> in the electron transfer system]<br/>
|authors=Gnaiger Erich
|authors=Gnaiger Erich
|year=2023
|year=2023
|journal=MitoFit Prep
|journal=MitoFit Prep
|abstract=[[File:CII-ambiguities Graphical abstract.png|200px|left]]
|abstract=[[File:CII-ambiguities Graphical abstract.png|150px|left]]
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.<br>
::: Gnaiger E (2024) Complex II ambiguities ā€• FADH<sub>2</sub> in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470
|keywords=coenzyme Q junction; Complex CII; electron transfer system; fatty acid oxidation; flavin adenine dinucleotide;
::: <small>Version 6 (v6) 2023-06-21 </small>
succinate dehydrogenase; tricarboxylic acid cycle
::: <small>Version 5 (v5) 2023-05-31, (v4) 2023-05-12, (v3) 2023-05-04, (v2) 2023-04-04, (v1) 2023-03-24 - [https://wiki.oroboros.at/index.php/File:Gnaiger_2023_MitoFit_CII.pdf Ā»Link to all versionsĀ«]</small>
The prevailing notion that reduced cofactors NADH and FADH<sub>2</sub> transfer electrons from the tricarboxylic acid cycle to the mitochondrial electron transfer system creates ambiguities regarding respiratory Complex II (CII). The succinate dehydrogenase subunit SDHA of CII oxidizes succinate and reduces the covalently bound prosthetic group FAD to FADH<sub>2</sub> in the canonical forward tricarboxylic acid cycle. However, several graphical representations of the electron transfer system depict FADH<sub>2</sub> in the mitochondrial matrix as a substrate to be oxidized by CII. This leads to the false conclusion that FADH<sub>2</sub> from the Ī²-oxidation cycle in fatty acid oxidation feeds electrons into CII. In reality, dehydrogenases of fatty acid oxidation channel electrons to the coenzyme Q-junction but not through CII. The ambiguities surrounding Complex II in the literature and educational resources call for quality control, to secure scientific standards in current communications of bioenergetics, and ultimately support adequate clinical applications. This review aims to raise awareness of the inherent '''[[ambiguity crisis]]''', complementing efforts to address the well-acknowledged issues of credibility and reproducibility.
<br>
|keywords=[[coenzyme]]; [[cofactor]]; [[prosthetic group]]; coenzyme Q junction, Q-junction; Complex II, CII; [[H+-linked electron transfer |H<sup>+</sup>-linked electron transfer]]; [[electron transfer system]], ETS; [[matrix-ETS]]; [[membrane-ETS]]; fatty acid oxidation, FAO; flavin adenine dinucleotide, FAD/FADH<sub>2</sub>; nicotinamide adenine dinucleotide, NAD<sup>+</sup>/NADH; succinate dehydrogenase, SDH; tricarboxylic acid cycle, TCA; [[substrate]]; [[Gibbs force]]
|mipnetlab=AT Innsbruck Oroboros
|mipnetlab=AT Innsbruck Oroboros
}}
}}
__TOC__
::::'''Ā» ''Links:''''' [[Ambiguity crisis]], [[Complex II ambiguities]], [[:Category:Ambiguity crisis - NAD and H+ |Complex I and hydrogen ion ambiguities in the electron transfer system]]
:::: '''Acknowledgements''': I thank [[Cardoso Luiza HD |Luiza H.D. Cardoso]], [[Schmitt Sabine |Sabine Schmitt]], and [[Donnelly Chris |Chris Donnelly]] for stimulating discussions, and [[Cocco Paolo |Paolo Cocco]] for expert help on the graphical abstract and Figures 1d and e. The constructive comments of an anonymous reviewer (J Biol Chem) are explicitly acknowledged. Contribution to the European Unionā€™s Horizon 2020 research and innovation program Grant 857394 ([[FAT4BRAIN]]).


ORC'''ID''': [[File:ORCID.png|20px|link=https://orcid.org/0000-0003-3647-5895]] Gnaiger Erich
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== Supplement: FADH<sub>2</sub> or FADH as substrate of CII in websites ==
Ā 
:::: Complex II ambiguities in graphical representations on FADH<sub>2</sub> as a substrate of Complex II in the canonical forward electron transfer. FADH ā†’ FAD+H ('''g'''), FADH<sub>2</sub> ā†’ FAD+2H<sup>+</sup> ('''aā€™''', '''c''', '''h-n'''), and FADH<sub>2</sub> ā†’ FAD ('''a''', '''b''', '''d-f''', '''o-Īø''') should be corrected to FADH<sub>2</sub> ā†’ FAD (Eq. 3b). NADH ā†’ NAD<sup>+</sup> is frequently written in graphs without showing the H<sup>+</sup> on the left side of the arrow, except for ('''p-r'''). NADH ā†’ NAD<sup>+</sup>+H<sup>+</sup> ('''a-g''', '''m'''), NADH ā†’ NAD<sup>+</sup>+2H<sup>+</sup> ('''h-l'''), NADH+H<sup>+</sup> ā†’ NAD<sup>+</sup>+2H<sup>+</sup> ('''j''', '''k'''), and NADH ā†’ NAD ('''Ī¹''') should be corrected to NADH+H<sup>+</sup> ā†’ NAD<sup>+</sup> (Eq. 3a). (Retrieved 2023-03-21 to 2023-05-04).
Ā 
:::::: [[File:OpenStax Biology.png|400px]]
::: ('''a''')
:::: '''Website 1''' ('''a''','''b'''): [https://openstax.org/books/biology/pages/7-4-oxidative-phosphorylation 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.
:::: '''Website 2''' ('''a''','''b'''): [https://opentextbc.ca/biology/chapter/4-3-citric-acid-cycle-and-oxidative-phosphorylation/ Concepts of Biology] - 1st Canadian Edition by Charles Molnar and Jane Gair - Fig. 4.19a
:::: '''Website 3''' ('''a''','''b'''): [https://www.pharmaguideline.com/2022/01/electron-transport-chain.html Pharmaguideline]
:::: '''Website 4''' ('''a''','''b'''): [https://www.texasgateway.org/resource/74-oxidative-phosphorylation Texas Gateway] - Figure 7.11
:::: '''Website 5''' ('''a''','''b'''): [https://opened.cuny.edu/courseware/lesson/639/overview - CUNY]
:::: '''Website 6''' ('''a''','''b'''): [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 1
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:::: '''Website 8''' ('''a'''): [https://brainbrooder.com/lesson/254/7-4-1-electron-transport-chain - Brain Brooder]
Ā 
:::::: [[File:Khan Academy modified from OpenStax CORRECTION.png|400px]]
::: ('''aā€™''')
:::: '''Website 9''' ('''aā€™''','''b''','''v'''): [https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc Khan Academy] - Image modified from "Oxidative phosphorylation: Figure 1", by OpenStax College, Biology (CC BY 3.0). Figure and text underscore the FADH<sub>2</sub>-error: "''FADH<sub>2</sub> .. feeds them ''(electrons)'' into the transport chain through complex II.''"
:::: '''Website 10''' ('''aā€™''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
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:::::: [[File:Expii OpenStax CORRECTION.png|400px]]
::: ('''b''')
:::: '''Website 1''' ('''a''','''b'''): [https://openstax.org/books/biology/pages/7-4-oxidative-phosphorylation OpenStax Biology] - Fig. 7.12
:::: '''Website 2''' ('''a''','''b'''): [https://opentextbc.ca/biology/chapter/4-3-citric-acid-cycle-and-oxidative-phosphorylation/ Concepts of Biology] - 1st Canadian Edition by Charles Molnar and Jane Gair - Fig. 4.19c
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:::: '''Website 4''' ('''a''','''b'''): [https://www.texasgateway.org/resource/74-oxidative-phosphorylation Texas Gateway] - Figure 7.13
:::: '''Website 5''' ('''a''','''b'''): [https://opened.cuny.edu/courseware/lesson/639/overview - CUNY]
:::: '''Website 6''' ('''a''','''b'''): [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 3
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:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
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:::::: [[File:Biologydictionary.net CORRECTION.png|400px]]
::: ('''c''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
:::: '''Website 12''' ('''c''','''t'''): [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo] - extender01 / iStock / Getty Images Plus
:::: '''Website 13''' ('''c'''): [https://commons.wikimedia.org/w/index.php?curid=30148497 wikimedia 30148497 - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, 2013-06-19]
:::: '''Website 14''' ('''c'''): [https://biologydictionary.net/electron-transport-chain-and-oxidative-phosphorylation/ biologydictionary.net 2018-08-21]
:::: '''Website 15''' ('''c'''): [https://www.quora.com/Why-does-FADH2-form-2-ATP Quora]
:::: '''Website 16''' ('''c'''): [https://teachmephysiology.com/biochemistry/atp-production/electron-transport-chain/ TeachMePhysiology] - Fig. 1. 2023-03-13
:::: '''Website 17''' ('''c'''): [https://www.toppr.com/ask/question/short-long-answer-types-whatis-the-electron-transport-system-and-what-are-its-functions/ toppr]
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:::::: [[File:Labxchange CORRECTION.png|400px]]
::: ('''d''')
:::: '''Website 18''' ('''d'''): [https://www.labxchange.org/library/items/lb:LabXchange:005ad47f-7556-3887-b4a6-66e74198fbcf:html:1 Labxchange] - Figure 8.15 credit: modification of work by Klaus Hoffmeier
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:::::: [[File:Jack Westin CORRECTION.png|400px]]
::: ('''e''')
:::: '''Website 19''' ('''e'''): [https://jackwestin.com/resources/mcat-content/oxidative-phosphorylation/electron-transfer-in-mitochondria Jack Westin MCAT Courses]
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:::::: [[File:Videodelivery CORRECTION.png|400px]]
::: ('''f''')
:::: '''Website 20''' ('''f'''): [https://videodelivery.net/79e91c40bf96f9692560fa378c5086b6/thumbnails/thumbnail.jpg videodelivery]
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:::::: [[File:SparkNotes CORRECTION.png|400px]]
::: ('''g''')
:::: '''Website 21''' ('''g'''): [https://www.sparknotes.com/biology/cellrespiration/oxidativephosphorylation/section2/ - SparkNotes]
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:::::: [[File:Researchtweet CORRECTION.png|400px]]
::: ('''h''')
:::: '''Website 22''' ('''h''','''t'''): [https://researchtweet.com/mitochondrial-electron-transport-chain-2/ researchtweet]
:::: '''Website 23''' ('''h'''): [https://microbenotes.com/electron-transport-chain/ Microbe Notes]
Ā 
:::::: [[File:FlexBooks 2 0 CORRECTION.png|400px]]
::: ('''i''')
:::: '''Website 24''' ('''i'''): [https://flexbooks.ck12.org/cbook/ck-12-biology-flexbook-2.0/section/2.28/primary/lesson/electron-transport-bio/ FlexBooks] - CK-12 Biology for High School- 2.28 Electron Transport, Figure 2
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:::::: [[File:Labster Theory CORRECTION.png|400px]]
::: ('''j''')
:::: '''Website 25''' ('''j'''): [https://theory.labster.com/Electron_Transport_Chain/ Labster Theory]
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:::::: [[File:Nau.edu CORRECTION.png|400px]]
::: ('''k''')
:::: '''Website 26''' ('''k'''): [https://www2.nau.edu/~fpm/bio205/u4fg36.html nau.edu]
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:::::: [[File:ScienceFacts CORRECTION.png|400px]]
::: ('''l''')
:::: '''Website 27''' ('''l'''): [https://www.sciencefacts.net/electron-transport-chain.html ScienceFacts]
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:::::: [[File:Ck12 CORRECTION.png|400px]]
::: ('''m''')
:::: '''Website 28''' ('''m'''): [https://www.ck12.org/biology/electron-transport/lesson/The-Electron-Transport-Chain-Advanced-BIO-ADV/ cK-12]
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:::::: [[File:Wikimedia ETC CORRECTION.png|400px]]
::: ('''n''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
:::: '''Website 29''' ('''n'''): [https://commons.wikimedia.org/wiki/File:Mitochondrial_electron_transport_chain.png Wikimedia]
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:::::: [[File:Creative-biolabs CORRECTION.png|400px]]
::: ('''o''')
:::: '''Website 30''' ('''o'''): [https://www.creative-biolabs.com/drug-discovery/therapeutics/electron-transport-chain.htm creative-biolabs]
Ā 
:::::: [[File:Vector Mine CORRECTION.png|400px]]
::: ('''p''')
:::: '''Website 31''' ('''p'''): [https://www.dreamstime.com/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram-electron-transport-chain-as-respiratory-embedded-image235345232 dreamstime]
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Ā 
:::::: [[File:YouTube Dirty Medicine Biochemistry CORRECTION.png|400px]]
::: ('''q''')
:::: '''Website 33''': [https://www.google.com/imgres?imgurl=https%3A%2F%2Fi.ytimg.com%2Fvi%2FLsRQ5_EmxJA%2Fmaxresdefault.jpg&tbnid=6w-0DVPMw7vOdM&vet=12ahUKEwjw2YO5--T9AhUwpCcCHduuDVgQMygDegUIARDzAQ..i&imgrefurl=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DLsRQ5_EmxJA&docid=bZxQYNch1Ys-VM&w=1280&h=720&q=electron%20transport%20chain&hl=en-US&client=firefox-b-d&ved=2ahUKEwjw2YO5--T9AhUwpCcCHduuDVgQMygDegUIARDzAQ YouTube Dirty Medicine Biochemistry] - Uploaded 2019-07-18
Ā 
:::::: [[File:DBriers CORRECTION.png|400px]]
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:::: '''Website 34''' ('''r'''): [http://www.dbriers.com/tutorials/ DBriers]
Ā 
:::::: [[File:SNC1D CORRECTION.png|400px]]
::: ('''s''')
:::: '''Website 35''' ('''s'''): [https://sbi4uraft2014.weebly.com/electron-transport-chain.html SNC1D - BIOLOGY LESSON PLAN BLOG]
Ā 
:::::: [[File:ThoughtCo-Getty Images CORRECTION.png|400px]]
::: ('''t''')
:::: '''Website 12''' ('''c''','''t'''): [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo] - extender01 / iStock / Getty Images Plus
:::: '''Website 22''' ('''h''','''t'''): [https://researchtweet.com/mitochondrial-electron-transport-chain-2/ researchtweet]
:::: '''Website 36''' ('''t'''): [https://www.dreamstime.com/royalty-free-stock-photography-electron-transport-chain-illustration-oxidative-phosphorylation-image36048617 dreamstime]
Ā 
:::::: [[File:Hyperphysics CORRECTION.png|400px]]
::: ('''u''')
:::: '''Website 37''' ('''u'''): [http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/Complex1.html hyperphysics]
Ā 
:::::: [[File:Khan Academy CORRECTION.png|400px]]
::: ('''v''')
:::: '''Website 9''' ('''aā€™''','''b''','''v'''): [https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc Khan Academy]
:::: '''Website 10''' ('''aā€™''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
Ā 
:::::: [[File:Expii-Whitney, Rolfes 2002 CORRECTION.png|400px]]
::: ('''w''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Whitney, Rolfes 2002
Ā 
:::::: [[File:UrbanPro CORRECTION.png|400px]]
::: ('''x''')
:::: '''Website 38''' ('''x'''): [https://www.urbanpro.com/ba-tuition/oxidative-phosphorylation UrbanPro]
Ā 
:::::: [[File:Quizlet CORRECTION.png|400px]]
::: ('''y''')
:::: '''Website 39''' ('''y'''): [https://quizlet.com/245664214/electron-transport-chain-facts-of-cell-respiration-diagram/ Quizlet]
Ā 
:::::: [[File:Unm.edu CORRECTION.png|400px]]
::: ('''z''')
:::: '''Website 40''' ('''z'''): [https://www.unm.edu/~lkravitz/Exercise%20Phys/ETCstory.html unm.edu]
Ā 
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::: ('''Ī±''')
:::: '''Website 41''' ('''Ī±'''): [https://www.google.com/imgres?imgurl=https%3A%2F%2Fi.ytimg.com%2Fvi%2FVER6xW_r1vc%2Fmaxresdefault.jpg&tbnid=Brshl0oN9LyYnM&vet=12ahUKEwjjlKSKpOX9AhWjmycCHbvGC34QMygWegUIARDWAQ..i&imgrefurl=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DVER6xW_r1vc&docid=VgTgrLf24Lzg4M&w=1280&h=720&itg=1&q=FADH2%20is%20the%20substrates%20of%20Complex%20II&hl=en&client=firefox-b-d&ved=2ahUKEwjjlKSKpOX9AhWjmycCHbvGC34QMygWegUIARDWAQ YouTube sciencemusicvideos] - Uploaded 2014-08-19
Ā 
:::::: [[File:Expii-Gabi Slizewska CORRECTION.png|400px]]
::: ('''Ī²''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii expii] - Image source: By Gabi Slizewska
Ā 
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:::: '''Website 42''' ('''Ī³'''): [https://biochemden.com/electron-transport-chain-mechanism/ BiochemDen.com]
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:::: '''Website 43''' ('''Ī“'''): [https://hopes.stanford.edu/riboflavin/ hopes, Huntingtonā€™s outreach project for education, at Stanford]
Ā 
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::: ('''Īµ''')
:::: '''Website 44''' ('''Īµ'''): [ https://www.studocu.com/en-gb/document/university-college-london/mammalian-physiology/electron-transport-chain/38063777 studocu, University College London]
Ā 
:::::: [[File:ScienceDirect CORRECTION.png|400px]]
::: ('''Ī¶''')
:::: '''Website 45''' ('''Ī¶'''): [https://www.google.com/imgres?imgurl=https%3A%2F%2Fars.els-cdn.com%2Fcontent%2Fimage%2F3-s2.0-B9780128008836000215-f21-07-9780128008836.jpg&imgrefurl=https%3A%2F%2Fwww.sciencedirect.com%2Ftopics%2Fengineering%2Felectron-transport-chain&tbnid=g3dD4u8Tvd6TWM&vet=12ahUKEwjc9deUprT9AhVxhv0HHXZbAd0QMygCegUIARDBAQ..i&docid=Moj_2_W0OpUDcM&w=632&h=439&q=FADH2%20is%20the%20substrates%20of%20Complex%20II&client=firefox-b-d&ved=2ahUKEwjc9deUprT9AhVxhv0HHXZbAd0QMygCegUIARDBAQ ScienceDirect]
Ā 
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:::: '''Website 46''' ('''Ī·'''): [https://www.bbc.co.uk/bitesize/guides/zdq9382/revision/5 BBC BITESIZE cK-12]
Ā 
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::: ('''Īø''')
:::: '''Website 47''' ('''Īø'''): [https://www.freepik.com/premium-vector/oxidative-phosphorylation-process-electron-transport-chain-final-step-cellular-respiration_29211885.htm freepik]
Ā 
:::::: [[File:LibreTexts Chemistry_CORRECTION.png|400px]]
::: ('''Ī¹''')
:::: '''Website 48''' ('''Ī¹'''): [https://chem.libretexts.org/Courses/Saint_Marys_College_Notre_Dame_IN/CHEM_118_(Under_Construction)/CHEM_118_Textbook/12%3A_Metabolism_(Biological_Energy)/12.4%3A_The_Citric_Acid_Cycle_and_Electron_Transport - LibreTexts Chemistry] - The Citric Acid Cycle and Electron Transport ā€“ Fig. 12.4.3
Ā 
:::::: [[File:Stillway LW CORRECTION.png|300px]]
:::: '''xx''' Stillway L William (2017) CHAPTER 9 Bioenergetics and Oxidative Metabolism. In: [https://doctorlib.info/medical/biochemistry/11.html Medical Biochemistry]
<br>
Ā 
Ā 
<big>'''from FAO and CII ambiguitiy to CII as a H<sup>+</sup> in websites'''</big>
Ā 
:::::: [[File:CHM333 LECTURES CORRECTION.png|250px]]
:::: '''xx''' [https://www.chem.purdue.edu/courses/chm333/Spring%202013/Lectures/Spring%202013%20Lecture%2037%20-%2038.pdf CHM333 LECTURES 37 & 38: 4/27 ā€“ 29/13 SPRING 2013 Professor Christine Hrycyna]
<br>
Ā 
(retrieved 2023-03-21 to 2023-05-02)
:::: '''Website 49''': [https://conductscience.com/electron-transport-chain/ Conduct Science]: "In Complex II, the enzyme succinate dehydrogenase in the inner mitochondrial membrane reduce FADH<sub>2</sub> to FAD<sup>+</sup>. Simultaneously, succinate, an intermediate in the Krebs cycle, is oxidized to fumarate." - Comments: FAD does not have a postive charge. FADH<sub>2</sub> is the reduced form, it is not reduced. And again: In CII, FAD is reduced to FADH<sub>2</sub>.
Ā 
:::: '''Website 50''': [https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/ The Medical Biochemistry Page]: ā€˜In addition to transferring electrons from the FADH<sub>2</sub> generated by SDH, complex II also accepts electrons from the FADH<sub>2</sub> generated during fatty acid oxidation via the fatty acyl-CoA dehydrogenases and from mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) of the glycerol phosphate shuttleā€™ (Figure 8d).
Ā 
:::: '''Website 51''': [https://www.chem.purdue.edu/courses/chm333/Spring%202013/Lectures/Spring%202013%20Lecture%2037%20-%2038.pdf CHM333 LECTURES 37 & 38: 4/27 ā€“ 29/13 SPRING 2013 Professor Christine Hrycyna]: Acyl-CoA dehydrogenase is listed under 'Electron transfer in Complex II'.
Ā 
Ā 
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:::: '''xx''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii expii - Image source: By Gabi Slizewska]: ā€˜FADH<sub>2</sub> from glycolysis and Krebs cycle is oxidized to FAD by Complex II. It also releases H<sup>+</sup> ions into the intermembrane space and passes off electronsā€™ (retrieved 2023-05-04).
Ā 
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:::::: [[File:BioNinja 2 CORRECTION.png|400px]]
:::: '''xx''': [https://ib.bioninja.com.au/higher-level/topic-8-metabolism-cell/untitled/electron-transport-chain.html BioNinja] (retrieved 2023-05-04).
Ā 
{{Template:Keywords: Substrates and cofactors}}
== Cited by ==
{{Template:Cited by Gnaiger 2024 MitoFit}}
[[Category:Ambiguity crisis - CII and FADH2]]
{{Labeling
{{Labeling
|area=
|area=Patients, mt-Awareness
|injuries=
|enzymes=Complex II;succinate dehydrogenase
|organism=
|additional=Ambiguity crisis, FAT4BRAIN, Publication:FAT4BRAIN
|tissues=
|preparations=
|topics=
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}}

Latest revision as of 08:48, 1 May 2024

Publications in the MiPMap
Gnaiger E (2023) Complex II ambiguities ā€• FADH2 in the electron transfer system. MitoFit Preprints 2023.3.v6. https://doi.org/10.26124/mitofit:2023-0003.v6 - Published 2023-11-22 J Biol Chem (2024)

Ā» MitoFit Preprints 2023.3.v6.

MitoFit pdf

Complex II ambiguities ā€• FADH2 in the electron transfer system

Gnaiger Erich (2023) MitoFit Prep

Abstract:

CII-ambiguities Graphical abstract.png
Gnaiger E (2024) Complex II ambiguities ā€• FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470
Version 6 (v6) 2023-06-21
Version 5 (v5) 2023-05-31, (v4) 2023-05-12, (v3) 2023-05-04, (v2) 2023-04-04, (v1) 2023-03-24 - Ā»Link to all versionsĀ«

The prevailing notion that reduced cofactors NADH and FADH2 transfer electrons from the tricarboxylic acid cycle to the mitochondrial electron transfer system creates ambiguities regarding respiratory Complex II (CII). The succinate dehydrogenase subunit SDHA of CII oxidizes succinate and reduces the covalently bound prosthetic group FAD to FADH2 in the canonical forward tricarboxylic acid cycle. However, several graphical representations of the electron transfer system depict FADH2 in the mitochondrial matrix as a substrate to be oxidized by CII. This leads to the false conclusion that FADH2 from the Ī²-oxidation cycle in fatty acid oxidation feeds electrons into CII. In reality, dehydrogenases of fatty acid oxidation channel electrons to the coenzyme Q-junction but not through CII. The ambiguities surrounding Complex II in the literature and educational resources call for quality control, to secure scientific standards in current communications of bioenergetics, and ultimately support adequate clinical applications. This review aims to raise awareness of the inherent ambiguity crisis, complementing efforts to address the well-acknowledged issues of credibility and reproducibility.
ā€¢ Keywords: coenzyme; cofactor; prosthetic group; coenzyme Q junction, Q-junction; Complex II, CII; H+-linked electron transfer; electron transfer system, ETS; matrix-ETS; membrane-ETS; fatty acid oxidation, FAO; flavin adenine dinucleotide, FAD/FADH2; nicotinamide adenine dinucleotide, NAD+/NADH; succinate dehydrogenase, SDH; tricarboxylic acid cycle, TCA; substrate; Gibbs force

ā€¢ O2k-Network Lab: AT Innsbruck Oroboros

Ā» Links: Ambiguity crisis, Complex II ambiguities, Complex I and hydrogen ion ambiguities in the electron transfer system
Acknowledgements: I thank Luiza H.D. Cardoso, Sabine Schmitt, and Chris Donnelly for stimulating discussions, and Paolo Cocco for expert help on the graphical abstract and Figures 1d and e. The constructive comments of an anonymous reviewer (J Biol Chem) are explicitly acknowledged. Contribution to the European Unionā€™s Horizon 2020 research and innovation program Grant 857394 (FAT4BRAIN).

Additions to 312 references on CII-ambiguities after publication of JBC 2024

Last update 2023-12-19
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Supplement: FADH2 or FADH as substrate of CII in websites

Complex II ambiguities in graphical representations on FADH2 as a substrate of Complex II in the canonical forward electron transfer. FADH ā†’ FAD+H (g), FADH2 ā†’ FAD+2H+ (aā€™, c, h-n), and FADH2 ā†’ FAD (a, b, d-f, o-Īø) should be corrected to FADH2 ā†’ FAD (Eq. 3b). NADH ā†’ NAD+ is frequently written in graphs without showing the H+ on the left side of the arrow, except for (p-r). NADH ā†’ NAD++H+ (a-g, m), NADH ā†’ NAD++2H+ (h-l), NADH+H+ ā†’ NAD++2H+ (j, k), and NADH ā†’ NAD (Ī¹) should be corrected to NADH+H+ ā†’ NAD+ (Eq. 3a). (Retrieved 2023-03-21 to 2023-05-04).
OpenStax Biology.png
(a)
Website 1 (a,b): 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.
Website 2 (a,b): Concepts of Biology - 1st Canadian Edition by Charles Molnar and Jane Gair - Fig. 4.19a
Website 3 (a,b): Pharmaguideline
Website 4 (a,b): Texas Gateway - Figure 7.11
Website 5 (a,b): - CUNY
Website 6 (a,b): lumen Biology for Majors I - Fig. 1
Website 7 (a): LibreTexts Biology Oxidative Phosphorylation - Electron Transport Chain - Figure 7.11.1
Website 8 (a): - Brain Brooder
Khan Academy modified from OpenStax CORRECTION.png
(aā€™)
Website 9 (aā€™,b,v): Khan Academy - Image modified from "Oxidative phosphorylation: Figure 1", by OpenStax College, Biology (CC BY 3.0). Figure and text underscore the FADH2-error: "FADH2 .. feeds them (electrons) into the transport chain through complex II."
Website 10 (aā€™,b,v): Saylor Academy
Expii OpenStax CORRECTION.png
(b)
Website 1 (a,b): OpenStax Biology - Fig. 7.12
Website 2 (a,b): Concepts of Biology - 1st Canadian Edition by Charles Molnar and Jane Gair - Fig. 4.19c
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Website 4 (a,b): Texas Gateway - Figure 7.13
Website 5 (a,b): - CUNY
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Website 40 (z): unm.edu
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(Ī±)
Website 41 (Ī±): YouTube sciencemusicvideos - Uploaded 2014-08-19
Expii-Gabi Slizewska CORRECTION.png
(Ī²)
Website 11 (b,c,n,w,Ī²): expii expii - Image source: By Gabi Slizewska
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(Ī³)
Website 42 (Ī³): BiochemDen.com
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(Ī“)
Website 43 (Ī“): hopes, Huntingtonā€™s outreach project for education, at Stanford
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(Īµ)
Website 44 (Īµ): [ https://www.studocu.com/en-gb/document/university-college-london/mammalian-physiology/electron-transport-chain/38063777 studocu, University College London]
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(Ī¶)
Website 45 (Ī¶): ScienceDirect
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(Ī·)
Website 46 (Ī·): BBC BITESIZE cK-12
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(Īø)
Website 47 (Īø): freepik
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(Ī¹)
Website 48 (Ī¹): - LibreTexts Chemistry - The Citric Acid Cycle and Electron Transport ā€“ Fig. 12.4.3
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xx Stillway L William (2017) CHAPTER 9 Bioenergetics and Oxidative Metabolism. In: Medical Biochemistry



from FAO and CII ambiguitiy to CII as a H+ in websites

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xx CHM333 LECTURES 37 & 38: 4/27 ā€“ 29/13 SPRING 2013 Professor Christine Hrycyna


(retrieved 2023-03-21 to 2023-05-02)
Website 49: Conduct Science: "In Complex II, the enzyme succinate dehydrogenase in the inner mitochondrial membrane reduce FADH2 to FAD+. Simultaneously, succinate, an intermediate in the Krebs cycle, is oxidized to fumarate." - Comments: FAD does not have a postive charge. FADH2 is the reduced form, it is not reduced. And again: In CII, FAD is reduced to FADH2.
Website 50: The Medical Biochemistry Page: ā€˜In addition to transferring electrons from the FADH2 generated by SDH, complex II also accepts electrons from the FADH2 generated during fatty acid oxidation via the fatty acyl-CoA dehydrogenases and from mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) of the glycerol phosphate shuttleā€™ (Figure 8d).
Website 51: CHM333 LECTURES 37 & 38: 4/27 ā€“ 29/13 SPRING 2013 Professor Christine Hrycyna: Acyl-CoA dehydrogenase is listed under 'Electron transfer in Complex II'.


Expii-Gabi Slizewska CORRECTION.png
xx: expii expii - Image source: By Gabi Slizewska: ā€˜FADH2 from glycolysis and Krebs cycle is oxidized to FAD by Complex II. It also releases H+ ions into the intermembrane space and passes off electronsā€™ (retrieved 2023-05-04).
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xx: BioNinja (retrieved 2023-05-04).


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Click to expand or collaps
Bioblast links: Substrates and cofactors - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
Substrate
Ā» Substrate
Ā» Product
Ā» Substrates as electron donors
Ā» Cellular substrates
Ā» MitoPedia: Substrates and metabolites
Ā» Substrate-uncoupler-inhibitor titration
Cofactor
Ā» Cofactor
Ā» Coenzyme, cosubstrate
Ā» Nicotinamide adenine dinucleotide
Ā» Coenzyme Q2
Ā» Prosthetic group
Ā» Flavin adenine dinucleotide
Referennces
Ā» Gnaiger E (2023) Complex II ambiguities ā€• FADH2 in the electron transfer system. MitoFit Preprints 2023.3.v6. https://doi.org/10.26124/mitofit:2023-0003.v6


Cited by

Gnaiger 2024 Ambiguity crisis.jpg
Gnaiger E (2024) Addressing the ambiguity crisis in bioenergetics and thermodynamics. MitoFit Preprints 2024.3. https://doi.org/10.26124/mitofit:2024-0003


Labels: MiParea: Patients, mt-Awareness 



Enzyme: Complex II;succinate dehydrogenase 



Ambiguity crisis, FAT4BRAIN, Publication:FAT4BRAIN 

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