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. | |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. | |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| | |abstract=[[File:CII-ambiguities Graphical abstract.png|150px|left]] | ||
::: < | ::: 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 | ||
::: <small>Version | ::: <small>Version 6 (v6) 2023-06-21 </small> | ||
The | ::: <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> | <br> | ||
|keywords=coenzyme Q junction; Complex CII; electron transfer system; fatty acid oxidation; flavin adenine dinucleotide; | |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]] | ||
succinate dehydrogenase; tricarboxylic acid cycle | |||
|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 Unionās 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: FADH<sub>2</sub> or FADH as substrate of CII in websites == | |||
: | |||
:::: | :::: 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). | ||
:::::: [[File: | :::::: [[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 | |||
:::: '''Website 7''' ('''a'''): [https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.11%3A_Oxidative_Phosphorylation_-_Electron_Transport_Chain LibreTexts Biology] Oxidative Phosphorylation - Electron Transport Chain - Figure 7.11.1 | |||
:::: '''Website 8''' ('''a'''): [https://brainbrooder.com/lesson/254/7-4-1-electron-transport-chain - Brain Brooder] | |||
:::::: [[File: | :::::: [[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] | |||
:::::: [[File: | :::::: [[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 | |||
:::: '''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 7.13 | |||
:::: '''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 | |||
:::: '''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 3," by Openstax College, Biology (CC BY 3.0) | |||
:::: '''Website 10''' ('''aā''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy] | |||
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax | |||
:::::: [[File: | :::::: [[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] | |||
:::::: [[File: | :::::: [[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 | |||
:::::: [[File: | :::::: [[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] | |||
:::::: [[File: | :::::: [[File:Videodelivery CORRECTION.png|400px]] | ||
:::: ''' | ::: ('''f''') | ||
:::: '''Website 20''' ('''f'''): [https://videodelivery.net/79e91c40bf96f9692560fa378c5086b6/thumbnails/thumbnail.jpg videodelivery] | |||
:::::: [[File: | :::::: [[File:SparkNotes CORRECTION.png|400px]] | ||
::: | ::: ('''g''') | ||
:::: '''Website 21''' ('''g'''): [https://www.sparknotes.com/biology/cellrespiration/oxidativephosphorylation/section2/ - SparkNotes] | |||
:::: ''' | |||
:::::: [[File: | :::::: [[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] | |||
:::::: [[File: | :::::: [[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 | |||
:::::: [[File: | :::::: [[File:Labster Theory CORRECTION.png|400px]] | ||
:::: ''' | ::: ('''j''') | ||
:::: '''Website 25''' ('''j'''): [https://theory.labster.com/Electron_Transport_Chain/ Labster Theory] | |||
:::::: [[File: | :::::: [[File:Nau.edu CORRECTION.png|400px]] | ||
::: | ::: ('''k''') | ||
:::: '''Website 26''' ('''k'''): [https://www2.nau.edu/~fpm/bio205/u4fg36.html nau.edu] | |||
:::::: [[File: | :::::: [[File:ScienceFacts CORRECTION.png|400px]] | ||
:::: ''' | ::: ('''l''') | ||
:::: '''Website 27''' ('''l'''): [https://www.sciencefacts.net/electron-transport-chain.html ScienceFacts] | |||
:::::: [[File: | :::::: [[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] | |||
:::::: [[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] | |||
:::: ''' | :::::: [[File:Creative-biolabs CORRECTION.png|400px]] | ||
::: ('''o''') | |||
:::: '''Website 30''' ('''o'''): [https://www.creative-biolabs.com/drug-discovery/therapeutics/electron-transport-chain.htm creative-biolabs] | |||
:::::: [[File: | :::::: [[File:Vector Mine CORRECTION.png|400px]] | ||
::: | ::: ('''p''') | ||
:::: '''Website | :::: '''Website 31''' ('''p'''): [https://www.dreamstime.com/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram-electron-transport-chain-as-respiratory-embedded-image235345232 dreamstime] | ||
:::: '''Website 32''' ('''p'''): [https://vectormine.com/item/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram/ VectorMine] | |||
:::: '''Website | |||
:::::: [[File: | :::::: [[File:YouTube Dirty Medicine Biochemistry CORRECTION.png|400px]] | ||
::: | ::: ('''q''') | ||
:::: '''Website | :::: '''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 | ||
:::::: [[File: | :::::: [[File:DBriers CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''r''') | ||
:::: '''Website 34''' ('''r'''): [http://www.dbriers.com/tutorials/ DBriers] | |||
:::::: [[File: | :::::: [[File:SNC1D CORRECTION.png|400px]] | ||
::: | ::: ('''s''') | ||
:::: '''Website | :::: '''Website 35''' ('''s'''): [https://sbi4uraft2014.weebly.com/electron-transport-chain.html SNC1D - BIOLOGY LESSON PLAN BLOG] | ||
:::::: [[File: | :::::: [[File:ThoughtCo-Getty Images CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''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] | |||
:::::: [[File: | :::::: [[File:Hyperphysics CORRECTION.png|400px]] | ||
::: | ::: ('''u''') | ||
:::: '''Website | :::: '''Website 37''' ('''u'''): [http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/Complex1.html hyperphysics] | ||
:::::: [[File: | :::::: [[File:Khan Academy CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''v''') | ||
:::: '''Website | :::: '''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] | |||
:::::: [[File: | :::::: [[File:Expii-Whitney, Rolfes 2002 CORRECTION.png|400px]] | ||
::: | ::: ('''w''') | ||
Ā | :::: '''Website 11''' ('''b''','''c''','''n''','''w''','''Ī²'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Whitney, Rolfes 2002 | ||
:::: '''Website | |||
:::::: [[File: | :::::: [[File:UrbanPro CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''x''') | ||
:::: '''Website 38''' ('''x'''): [https://www.urbanpro.com/ba-tuition/oxidative-phosphorylation UrbanPro] | |||
:::::: [[File: | :::::: [[File:Quizlet CORRECTION.png|400px]] | ||
::: | ::: ('''y''') | ||
:::: '''Website | :::: '''Website 39''' ('''y'''): [https://quizlet.com/245664214/electron-transport-chain-facts-of-cell-respiration-diagram/ Quizlet] | ||
:::::: [[File: | :::::: [[File:Unm.edu CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''z''') | ||
:::: '''Website 40''' ('''z'''): [https://www.unm.edu/~lkravitz/Exercise%20Phys/ETCstory.html unm.edu] | |||
:::::: [[File: | :::::: [[File:YouTube sciencemusicvideos CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''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 | |||
:::::: [[File: | :::::: [[File:Expii-Gabi Slizewska CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''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 | |||
:::::: [[File: | :::::: [[File:BiochemDen CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''Ī³''') | ||
:::: '''Website 42''' ('''Ī³'''): [https://biochemden.com/electron-transport-chain-mechanism/ BiochemDen.com] | |||
:::::: [[File: | :::::: [[File:Hopes CORRECTION.png|400px]] | ||
:::: '''Website | :::('''Ī“''') | ||
:::: '''Website 43''' ('''Ī“'''): [https://hopes.stanford.edu/riboflavin/ hopes, Huntingtonās outreach project for education, at Stanford] | |||
:::::: [[File: | :::::: [[File:Studocu CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''Īµ''') | ||
:::: '''Website 44''' ('''Īµ'''): [ https://www.studocu.com/en-gb/document/university-college-london/mammalian-physiology/electron-transport-chain/38063777 studocu, University College London] | |||
:::::: [[File:ScienceDirect CORRECTION.png|400px]] | :::::: [[File:ScienceDirect CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''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] | |||
:::::: [[File: | :::::: [[File:BBC BITESIZE CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''Ī·''') | ||
:::: '''Website 46''' ('''Ī·'''): [https://www.bbc.co.uk/bitesize/guides/zdq9382/revision/5 BBC BITESIZE cK-12] | |||
:::::: [[File: | :::::: [[File:Freepik CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''Īø''') | ||
:::: '''Website 47''' ('''Īø'''): [https://www.freepik.com/premium-vector/oxidative-phosphorylation-process-electron-transport-chain-final-step-cellular-respiration_29211885.htm freepik] | |||
:::::: [[File: | :::::: [[File:LibreTexts Chemistry_CORRECTION.png|400px]] | ||
:::: '''Website | ::: ('''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 | |||
:::::: [[File: | :::::: [[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> | |||
<big>'''from FAO and CII ambiguitiy to CII as a H<sup>+</sup> in websites'''</big> | |||
:::::: [[File: | :::::: [[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> | |||
(retrieved 2023-03-21 to 2023-05-02) | |||
:::: '''Website | :::: '''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>. | ||
:: | |||
:::: '''Website 50''': [https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/ The Medical Biochemistry Page]: āIn 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). | |||
:::: '''Website | |||
:::: '''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'. | |||
:::: '''Website | |||
:::::: [[File:Expii-Gabi Slizewska CORRECTION.png|400px]] | :::::: [[File:Expii-Gabi Slizewska CORRECTION.png|400px]] | ||
:::: ''' | :::: '''xx''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii expii - Image source: By Gabi Slizewska]: āFADH<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 | |||
:::::: [[File:BioNinja 1 CORRECTION.png|400px]] | |||
:::::: [[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). | |||
{{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 | ||
| | |enzymes=Complex II;succinate dehydrogenase | ||
|additional=Ambiguity crisis, FAT4BRAIN, Publication:FAT4BRAIN | |||
|additional=FAT4BRAIN | |||
}} | }} |
Latest revision as of 08:48, 1 May 2024
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.
Complex II ambiguities ā FADH2 in the electron transfer system
Gnaiger Erich (2023) MitoFit Prep
Abstract:
- 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 Unionās 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).
- (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
- (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
- (b)
- Website 1 (a,b): OpenStax Biology - Fig. 7.12
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- Website 5 (a,b): - CUNY
- Website 6 (a,b): lumen Biology for Majors I - Fig. 3
- Website 9 (aā,b,v): Khan Academy - Image modified from "Oxidative phosphorylation: Figure 3," by Openstax College, Biology (CC BY 3.0)
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- Website 11 (b,c,n,w,Ī²): expii - Image source: By CNX OpenStax
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- (Ī¶)
- Website 45 (Ī¶): ScienceDirect
- (Ī·)
- Website 46 (Ī·): BBC BITESIZE cK-12
- (Īø)
- Website 47 (Īø): freepik
- (Ī¹)
- Website 48 (Ī¹): - LibreTexts Chemistry - The Citric Acid Cycle and Electron Transport ā Fig. 12.4.3
- 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
(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: āIn 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'.
- xx: expii expii - Image source: By Gabi Slizewska: āFADH2 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).
- xx: BioNinja (retrieved 2023-05-04).
- Bioblast links: Substrates and cofactors - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
- Cofactor
- Ā» Cofactor
- Ā» Coenzyme, cosubstrate
- Ā» Nicotinamide adenine dinucleotide
- Ā» Coenzyme Q2
- Ā» Prosthetic group
- Ā» Flavin adenine dinucleotide
- Cofactor
- 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
- Referennces
Cited by
- 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