Gnaiger 2023 MitoFit CII: Difference between revisions

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{{Publication
{{Publication
|title=Gnaiger E (2023) Complex II ambiguities ― 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 ― 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 ― 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 ― 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 ― 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 »Link to all versions«]</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 β-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__
::::'''» ''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 Union’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
:::::: [[File:Bektas 2019 Aging (Albany NY) CORRECTION.png|400px|link=Bektas 2019 Aging (Albany NY)]]
:::: '''#1''' Bektas A, Schurman SH, Gonzalez-Freire M, Dunn CA, Singh AK, Macian F, Cuervo AM, Sen R, Ferrucci L (2019) Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy. '''Aging (Albany NY)''' 11:9234-63. - [[Bektas 2019 Aging (Albany NY) |»Bioblast link«]]


ORC'''ID''': [[File:ORCID.png|20px|link=https://orcid.org/0000-0003-3647-5895]] Gnaiger Erich
:::::: [[File:Ben-Shachar 2009 J Neural Transm (Vienna) CORRECTION.png|400px|link=Ben-Shachar 2009 J Neural Transm (Vienna)]]
:::: '''#2''' Ben-Shachar D (2009) The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia. '''J Neural Transm (Vienna)''' 116:1383-96. - [[Ben-Shachar 2009 J Neural Transm (Vienna) |»Bioblast link«]]
 
 
:::::: [[File:Bon 2022 J Clin Case Rep Stud CORRECTION.png|400px|link=Bon 2022 J Clin Case Rep Stud]]
:::: '''#3''' Bon E, Maksimovich NY, Dremza IK (2022) Alendronate-induced nephropathy. '''J Clin Case Rep Stud''' 3. - [[Bon 2022 J Clin Case Rep Stud |»Bioblast link«]]


__TOC__
== Is there a problem ? ==
:::::: [[File:Arnold, Finley 2022 Fig1.png|600px|link=Arnold 2023 J Biol Chem]]
:::: Ref. [1] Arnold PK, Finley LWS (2023) Regulation and function of the mammalian tricarboxylic acid cycle. J Biol Chem 299:102838. - [[Arnold 2023 J Biol Chem |»Bioblast link«]]
<br>


:::::: [[File:Elsaeed 2021 Medicine Updates CORRECTION.png|400px|link=Elsaeed 2021 Medicine Updates]]
:::: '''#4''' Elsaeed EM, Hamad A, Erfan OS, Elshahat M, Ebrahim F (2021) Role played by hippocampal apoptosis, autophagy and necroptosis in pathogenesis of diabetic cognitive dysfunction: a review of literature. '''Medicine Updates''' 6:41-63. - [[Elsaeed 2021 Medicine Updates |»Bioblast link«]]


== FADH<sub>2</sub> and FMNH<sub>2</sub> in the S- and N-pathways ==
[[File:N-S FADH2-FMNH2.png|right|400px]]
:::: Respiratory Complex CII participates both in the membrane-bound electron transfer system (membrane-ETS) and TCA cycle (matrix-ETS plus CII; [[BEC_2020.1_doi10.26124bec2020-0001.v1 |Gnaiger et al 2020]]). Branches of electron transfer from the reduced coenzyme NADH of nicotinamide adenine dinucleotide N and succinate S converge at the Q-junction in the ETS ('''Figure ;a''' modified from [[Gnaiger_2020_BEC_MitoPathways |Gnaiger 2020]]).


:::: The reduced flavin groups FADH<sub>2</sub> of flavin adenine dinucleotide and FMNH<sub>2</sub> of flavin mononucleotide are at functionally comparable levels in the electron transfer to Q from CII and CI, respectively, just as succinate and NADH are the comparable reduced substrates of CII and CI, respectively ([[Gnaiger_2020_BEC_MitoPathways |Gnaiger 2020]]). In CII the oxidized form FAD is reduced by succinate to the product FADH<sub>2</sub> and the oxidized product fumarate in the TCA cycle. In CI FMN is reduced by NADH forming FMNH<sub>2</sub> and the oxidized NAD<sup>+</sup>. FADH<sub>2</sub> and FMNH<sub>2</sub> are reoxidized downstream in CII and CI by electron transfer to Q in the membrane-bound ETS ('''Figure b''').
:::::: [[File:Facucho-Oliveira 2009 Stem Cell Rev Rep CORRECTION.png|400px|link=Facucho-Oliveira 2009 Stem Cell Rev Rep]]
:::: '''#5''' Facucho-Oliveira JM, St John JC (2009) The relationship between pluripotency and mitochondrial DNA proliferation during early embryo development and embryonic stem cell differentiation. '''Stem Cell Rev Rep''' 5:140-58. - [[Facucho-Oliveira 2009 Stem Cell Rev Rep |»Bioblast link«]]


:::: Ref. [2]  Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. https://doi.org/10.26124/bec:2020-0002
:::: Ref. [3]  Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. https://doi.org/10.26124/bec:2020-0001.v1


:::::: [[File:Iqbal 2014 Springer, New York CORRECTION.png|400px|link=Iqbal 2014 Springer, New York]]
:::: '''#6''' Iqbal T, Welsby PJ, Howarth FC, Bidasee K, Adeghate E, Singh J (2014) Effects of diabetes-induced hyperglycemia in the heart: biochemical and structural slterations. In: Turan B, Dhalla N (eds) Diabetic cardiomyopathy. Advances in biochemistry in health and disease 9. '''Springer''', New York. - [[Iqbal 2014 Springer, New York |»Bioblast link«]]


=== The source and consequence of Complex II ambiguities ===


:::: Ambiguities emerge if the presentation of a concept is vague to an extent that allows for equivocal interpretations. As a consequence of ambiguous representations, even a basically clear and quite simple concept may be communicated further without appropriate reflection as an erroneous divergence from an established truth. The following quotes from Cooper (2000) provide an example.
:::::: [[File:Keogh 2015 Biochim Biophys Acta CORRECTION.png|400px|link=Keogh 2015 Biochim Biophys Acta]]
:::: '''#7''' Keogh MJ, Chinnery PF (2015) Mitochondrial DNA mutations in neurodegeneration. '''Biochim Biophys Acta''' 1847:1401-11. - [[Keogh 2015 Biochim Biophys Acta |»Bioblast link«]]


:::::: [[File:Cooper 2000 Sunderland 10-9.png|700px]]
:::: Ref. [4]  Cooper GM (2000) The cell: a molecular approach. 2nd edition. Sunderland (MA): Sinauer Associates Available from: https://www.ncbi.nlm.nih.gov/books/NBK9885/  - [[Cooper 2000 Sunderland (MA): Sinauer Associates |»Bioblast link«]]
:::: (''1'') 'Electrons from NADH enter the electron transport chain in complex I, .. A distinct protein complex (complex II), which consists of four polypeptides, receives electrons from the citric acid cycle intermediate, succinate (Figure 10.9). These electrons are transferred to FADH<sub>2</sub>, rather than to NADH, and then to coenzyme Q.'
:::::: ''Comment'': Here, the frequent comparison is made between FADH<sub>2</sub> (linked to CII) and NADH (linked to CI).


:::: (''2'') 'In contrast to the transfer of electrons from NADH to coenzyme Q at complex I, the transfer of electrons from FADH<sub>2</sub> to coenzyme Q is not associated with a significant decrease in free energy and, therefore, is not coupled to ATP synthesis.'
:::::: [[File:Kunst 2023 Biomedicines CORRECTION.png|400px|link=Kunst 2023 Biomedicines]]
:::::: ''Comment'': Note that CI is '''''in''''' the path of the transfer of electrons from NADH to coenzyme Q. In contrast, the transfer of electrons from FADH<sub>2</sub> to coenzyme Q is '''''downstream''''' of CII. Thus even a large Gibbs force ('decrease in free energy') in FADH<sub>2</sub>→Q would fail to drive the coupled process of proton translocation through CII, since the Gibbs force in S→FADH<sub>2</sub> is missing. (In parentheses: None of these steps are coupled to ATP synthesis. Redox-driven proton translocation should not be confused with ''pmF''-driven phosphorylation of ADP).
:::: '''#8''' Kunst C, Schmid S, Michalski M, Tümen D, Buttenschön J, Müller M, Gülow K (2023) The influence of gut microbiota on oxidative stress and the immune system. '''Biomedicines''' 11:1388. - [[Kunst 2023 Biomedicines |»Bioblast link«]]


:::: (''3'') 'Electrons from succinate enter the electron transport chain via FADH<sub>2</sub> in complex II. They are then transferred to coenzyme Q and carried through the rest of the electron transport chain ..'
:::: ''Comment'': The ambiguity is caused by a lack of unequivocal definition of the electron transfer system ('electron transport chain'). CII receives electrons (''1'') from succinate, yet it is suggested that electrons (from succinate) enter the electron transport chain (''3'') via FADH<sub>2</sub> in complex II. Then two contrasting definitions are implied of the term 'electron transport chain' or better membrane-bound electron transfer system, membrane-ETS. (''a'') If CII is part of the membrane-ETS, then electrons enter the membrane-ETS from succinate (''1'') but not from FADH<sub>2</sub>. (''b'') If electrons enter the 'electron transport chain' via FADH<sub>2</sub> in Complex II (''3''), then CII would be upstream and hence not part of the membrane-ETS (to which conclusion, obviously - see '''Figure''' - nobody would agree). Dismissing concept (''b'') of the membrane-ETS, then remains the ambiguity, if electrons enter the membrane-ETS from FADH<sub>2</sub> (''3'', wrong) or from succinate (''1'', correct).


=== FADH<sub>2</sub> - FAD confusion in the S-pathway ===
:::::: [[File:Lal 2018 Springer CORRECTION.png|400px|link=Lal 2018 Springer]]
:::: '''#9''' Lal MA (2018) Respiration. In: Bhatla SC, Lal MA (eds) Plant physiology, development and metabolism. '''Springer''', Singapore:253-314. - [[Lal 2018 Springer |»Bioblast link«]]


:::: FADH<sub>2</sub> appears in several publications as the substrate of CII in the electron transfer system linked to succinate oxidation. It is surprising that this error is widely propagated particularly in the most recent literature. For clarification, see [[Gnaiger_2020_BEC_MitoPathways |Gnaiger (2020) page 48]].


:::: The following examples are listed chronologically and illustrate
:::::: [[File:Lane 2000 Pediatr Res CORRECTION.png|400px|link=Lane 2000 Pediatr Res]]
::::'''(1)''' '''ambiguities''' in graphical representations: '''FADH<sub>2</sub> is the product and substrate of CII''' in the same figure, e.g. DeBerardinis, Chandel (2016);
:::: '''#10''' Lane RH, Tsirka AE, Gruetzmacher EM (2000) Uteroplacental insufficiency alters cerebral mitochondrial gene expression and DNA in fetal and juvenile rats. '''Pediatr Res''' 47:792-7. - [[Lane 2000 Pediatr Res |»Bioblast link«]]
::::'''(2)''' '''evolving errors''' in graphical representations: e.g. from Figure 6 (ambiguity) to Figure 1 (error) in Chandel (2021);
::::'''(3)''' ambiguities with '''discrepancies between graphical representation and text''': e.g. Figure 1 (error) and text in Fisher-Wellman, Neufer (2012) - 'Reducing equivalents (NADH, FADH<sub>2</sub>) provide electrons that flow through complex I, the ubiquinone cycle (Q/QH<sub>2</sub>), complex III, cytochrome ''c'', complex IV, and to the final acceptor O<sub>2</sub> to form water' (correct);
::::'''(4)''' simple '''graphical errors''': e.g. Brownlee (2001), Yépez et al (2018), Chen et al (2022); to
::::'''(5)''' propagation of the '''error in the graphical representation solidified by text''': e.g. Arnold, Finley (2022) with the following quotes:
::::::* 'SDH reduces FAD to FADH<sub>2</sub>, which donates its electrons to complex II';
::::::* 'each complete turn of the TCA cycle generates three NADH and one FADH<sub>2</sub> molecules, which donate their electrons to complex I and complex II, respectively';
::::::* 'complex I and complex II oxidize NADH and FADH<sub>2</sub>, respectively'.


:::::: [[File:Arnold, Finley 2022 CORRECTION.png|600px|link=Arnold 2023 J Biol Chem]]
:::: Ref. [1] Arnold PK, Finley LWS (2023) Regulation and function of the mammalian tricarboxylic acid cycle. J Biol Chem 299:102838. - [[Arnold 2023 J Biol Chem |»Bioblast link«]]
<br>


:::::: [[File:Chen 2022 Am J Physiol Cell Physiol CORRECTION.png|500px|link=Chen 2022 Am J Physiol Cell Physiol]]
:::::: [[File:Palma 2023 Oncogene CORRECTION.png|400px|link=Palma 2023 Oncogene]]
:::: Ref. [5] 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. - [[Chen 2022 Am J Physiol Cell Physiol |»Bioblast link«]]
:::: '''#11''' Palma FR, Gantner BN, Sakiyama MJ, Kayzuka C, Shukla S, Lacchini R, Cunniff B, Bonini MG (2023) ROS production by mitochondria: function or dysfunction? '''Oncogene'''. - [[Palma 2023 Oncogene |»Bioblast link«]]
<br>


:::::: [[File:Turton 2022 Int J Mol Sci CORRECTION.png|500px|link=Turton 2022 Int J Mol Sci]]
:::: Ref. [6] Turton N, Cufflin N, Dewsbury M, Fitzpatrick O, Islam R, Watler LL, McPartland C, Whitelaw S, Connor C, Morris C, Fang J, Gartland O, Holt L, Hargreaves IP (2022) The biochemical assessment of mitochondrial respiratory chain disorders. Int J Mol Sci 23:7487. - [[Turton 2022 Int J Mol Sci |»Bioblast link«]]
<br>


:::::: [[File:Ahmad 2022 StatPearls CORRECTION.png|400px|link=Ahmad 2022 StatPearls Publishing]]
:::::: [[File:Quintard 2018 Springer, Cham CORRECTION.png|400px|link=Quintard 2018 Springer, Cham]]
:::: Ref. [7] Ahmad M, Wolberg A, Kahwaji CI (2022) Biochemistry, electron transport chain. StatPearls Publishing StatPearls [Internet]. Treasure Island (FL) - [[Ahmad 2022 StatPearls Publishing |»Bioblast link«]]
:::: '''#12''' Quintard H, Fontaine E, Ichai C (2018) Energy metabolism: from the organ to the cell. In: Ichai, C., Quintard, H., Orban, JC. (eds) Metabolic Disorders and Critically Ill Patients. '''Springer''', Cham. - [[Quintard 2018 Springer, Cham |»Bioblast link«]]
<br>


:::::: [[File:Yuan 2022 Oxid Med Cell Longev CORRECTION.png|500px|link=Yuan 2022 Oxid Med Cell Longev]]
:::: Ref. [8] 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. - [[Yuan 2022 Oxid Med Cell Longev |»Bioblast link«]]
<br>


:::: [[File:Chandel 2021 Cold Spring Harb Perspect Biol CORRECTION.png|1000px|link=Chandel 2021 Cold Spring Harb Perspect Biol]]  
:::::: [[File:Reiss 2022 Exp Gerontol CORRECTION.png|400px|link=Reiss 2022 Exp Gerontol]]
:::: Ref. [9] Chandel NS (2021) Mitochondria. Cold Spring Harb Perspect Biol 13:a040543. - [[Chandel 2021 Cold Spring Harb Perspect Biol |»Bioblast link«]]  
:::: '''#13''' Reiss AB, Ahmed S, Dayaramani C, Glass AD, Gomolin IH, Pinkhasov A, Stecker MM, Wisniewski T, De Leon J (2022) The role of mitochondrial dysfunction in Alzheimer's disease: A potential pathway to treatment. '''Exp Gerontol''' 164:111828. - [[Reiss 2022 Exp Gerontol |»Bioblast link«]]
<br>


:::::: [[File:Yin 2021 FASEB J CORRECTION.png|500px|link=Yin 2021 FASEB J]]
:::: Ref. [10] Yin M, O'Neill LAJ (2021) The role of the electron transport chain in immunity. FASEB J 35:e21974. - [[Yin 2021 FASEB J |»Bioblast link«]]


:::::: [[File:Missaglia 2021 CORRECTION.png|500px|link=Missaglia 2021 Crit Rev Biochem Mol Biol]]  
:::::: [[File:Saghiv 2020 Springer, Cham CORRECTION.png|400px|link=Saghiv 2020 Springer, Cham]]
:::: Ref. [11] Missaglia S, Tavian D, Angelini C (2021) ETF dehydrogenase advances in molecular genetics and impact on treatment. Crit Rev Biochem Mol Biol 56:360-72. - [[Missaglia 2021 Crit Rev Biochem Mol Biol |»Bioblast link«]]  
:::: '''#14''' Saghiv MS, Sagiv MS (2020) Metabolism. In: Basic Exercise Physiology. '''Springer''', Cham. - [[Saghiv 2020 Springer, Cham |»Bioblast link«]]
<br>


:::::: [[File:Gasmi 2021 Arch Toxicol CORRECTION.png|500px|link=Gasmi 2021 Arch Toxicol]]
:::: Ref. [12] Gasmi A, Peana M, Arshad M, Butnariu M, Menzel A, Bjørklund G (2021) Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis. Arch Toxicol 95:1161-78. - [[Gasmi 2021 Arch Toxicol |»Bioblast link«]]
<br>


:::::: [[File:Turton 2021 Expert Opinion Orphan Drugs CORRECTION.png|400px|link=Turton 2021 Expert Opinion Orphan Drugs]]
:::::: [[File:SiouNing 2023 Molecules CORRECTION.png|400px|link=SiouNing 2023 Molecules]]
:::: Ref. [13] Turton N, Bowers N, Khajeh S, Hargreaves IP, Heaton RA (2021) Coenzyme Q10 and the exclusive club of diseases that show a limited response to treatment. Expert Opinion on Orphan Drugs 9:151-60. - [[Turton 2021 Expert Opinion Orphan Drugs |»Bioblast link«]]
:::: '''#15''' SiouNing AS, Seong TS, Kondo H, Bhassu S (2023) MicroRNA regulation in infectious diseases and its potential as a biosensor in future aquaculture industry: a review. '''Molecules''' 28:4357. - [[SiouNing 2023 Molecules |»Bioblast link«]]
<br>


:::::: [[File:Martinez-Reyes, Chandel 2020 CORRECTION.png|600px|link=Martinez-Reyes 2020 Nat Commun]]
:::: Ref. [14] Martínez-Reyes I, Chandel NS (2020) Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 11:102. - [[Martinez-Reyes 2020 Nat Commun |»Bioblast link«]]
<br>


:::::: [[File:Raimondi 2020 Br J Cancer CORRECTION.png|400px|link=Raimondi 2020 Br J Cancer]]
:::::: [[File:St John 2012 Cell Tissue Res CORRECTION.png|400px|link=St John 2012 Cell Tissue Res]]
:::: Ref. [15] Raimondi V, Ciccarese F, Ciminale V (2020) Oncogenic pathways and the electron transport chain: a dangeROS liaison. Br J Cancer 122:168-81. - [[Raimondi 2020 Br J Cancer |»Bioblast link«]]
:::: '''#16''' St John JC (2012) Transmission, inheritance and replication of mitochondrial DNA in mammals: implications for reproductive processes and infertility. '''Cell Tissue Res''' 349:795-808. - [[St John 2012 Cell Tissue Res |»Bioblast link«]]
<br>


:::::: [[File:Morelli 2019 Open Biol CORRECTION.png|500px|link=Morelli 2019 Open Biol]]
:::: Ref. [16] Morelli AM, Ravera S, Calzia D, Panfoli I (2019) An update of the chemiosmotic theory as suggested by possible proton currents inside the coupling membrane. Open Biol 9:180221. - [[Morelli 2019 Open Biol |»Bioblast link«]]
<br>


:::::: [[File:Lewis 2019 CORRECTION.png|500px|link=Lewis 2019 Int J Mol Sci]]
:::::: [[File:Su 2020 Mol Biol Rep CORRECTION.png|400px|link=Su 2020 Mol Biol Rep]]
:::: Ref. [17] Lewis MT, Kasper JD, Bazil JN, Frisbee JC, Wiseman RW (2019) Quantification of mitochondrial oxidative phosphorylation in metabolic disease: application to Type 2 diabetes. Int J Mol Sci 20:5271. - [[Lewis 2019 Int J Mol Sci |»Bioblast link«]]
:::: '''#17''' Su J, Ye D, Gao C, Huang Q, Gui D (2020) Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury. '''Mol Biol Rep''' 47:8023-35. - [[Su 2020 Mol Biol Rep |»Bioblast link«]]
<br>


:::::: [[File:Sarmah 2019 Transl Stroke Res CORRECTION.png|500px|link=Sarmah 2019 Transl Stroke Res]]
:::: Ref. [18] Sarmah D, Kaur H, Saraf J, Vats K, Pravalika K, Wanve M, Kalia K, Borah A, Kumar A, Wang X, Yavagal DR, Dave KR, Bhattacharya P (2019) Mitochondrial dysfunction in stroke: implications of stem cell therapy. Transl Stroke Res doi: 10.1007/s12975-018-0642-y - [[Sarmah 2019 Transl Stroke Res |»Bioblast link«]]


:::::: [[File:Yepez 2018 PLOS One Fig1B.jpg|300px|link=Yepez 2018 PLOS One]]
:::::: [[File:Thorgersen 2022 Front Microbiol CORRECTION.png|400px|link=Thorgersen 2022 Front Microbiol]]
:::: Ref. [19] Yépez VA, Kremer LS, Iuso A, Gusic M, Kopajtich R, Koňaříková E, Nadel A, Wachutka L, Prokisch H, Gagneur J (2018) OCR-Stats: Robust estimation and statistical testing of mitochondrial respiration activities using Seahorse XF Analyzer. PLOS ONE 13:e0199938. - [[Yepez 2018 PLOS One |»Bioblast link«]]
:::: '''#18''' Thorgersen MP, Schut GJ, Poole FL 2nd, Haja DK, Putumbaka S, Mycroft HI, de Vries WJ, Adams MWW (2022) Obligately aerobic human gut microbe expresses an oxygen resistant tungsten-containing oxidoreductase for detoxifying gut aldehydes. '''Front Microbiol''' 13:965625. - [[Thorgersen 2022 Front Microbiol |»Bioblast link«]]
<br>


:::::: [[File:Chowdhury 2018 Oxid Med Cell Longev CORRECTION.png|400px|link=Chowdhury 2018 Oxid Med Cell Longev]]
:::: Ref. [20] Roy Chowdhury S, Banerji V (2018) Targeting mitochondrial bioenergetics as a therapeutic strategy for chronic lymphocytic leukemia. Oxid Med Cell Longev 2018:2426712. - [[Chowdhury 2018 Oxid Med Cell Longev |»Bioblast link«]]
<br>


:::::: [[File:De Villiers 2018 Adv Exp Med Biol CORRECTION.png|400px|link=De Villiers 2018 Adv Exp Med Biol]]
:::::: [[File:Venkatachalam 2022 Cells CORRECTION.png|400px|link=Venkatachalam 2022 Cells]]
:::: Ref. [21] de Villiers D, Potgieter M, Ambele MA, Adam L, Durandt C, Pepper MS (2018) The role of reactive oxygen species in adipogenic differentiation. Adv Exp Med Biol 1083:125-144. - [[De Villiers 2018 Adv Exp Med Biol |»Bioblast link«]]
:::: '''#19''' Venkatachalam K (2022) Regulation of aging and longevity by ion channels and transporters. '''Cells''' 11:1180. - [[Venkatachalam 2022 Cells |»Bioblast link«]]
<br>


:::::: [[File:Zhang 2018 Mil Med Res CORRECTION.png|400px|link=Zhang 2018 Mil Med Res]]
:::: Ref. [22] Zhang H, Feng YW, Yao YM (2018) Potential therapy strategy: targeting mitochondrial dysfunction in sepsis. Mil Med Res 5:41. - [[Zhang 2018 Mil Med Res |»Bioblast link«]]
<br>


:::::: [[File:Polyzos 2017 Mech Ageing Dev CORRECTION.png|400px|link=Polyzos 2017 Mech Ageing Dev]]
:::::: [[File:Wall 2006 Am J Physiol Heart Circ Physiol CORRECTION.png|400px|link=Wall 2006 Am J Physiol Heart Circ Physiol]]
:::: Ref. [23] Polyzos AA, McMurray CT (2017) The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington's disease. Mech Ageing Dev 161:181-97. - [[Polyzos 2017 Mech Ageing Dev |»Bioblast link«]]
:::: '''#20''' Wall JA, Wei J, Ly M, Belmont P, Martindale JJ, Tran D, Sun J, Chen WJ, Yu W, Oeller P, Briggs S, Gustafsson AB, Sayen MR, Gottlieb RA, Glembotski CC (2006) Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6. '''Am J Physiol Heart Circ Physiol''' 291:H2462-72. - [[Wall 2006 Am J Physiol Heart Circ Physiol |»Bioblast link«]]
<br>


:::::: [[File:Jones, Bennett 2017 Chapter 4 CORRECTION.png|400px|link=Jones 2017 Elsevier]]
:::: Ref. [24] Jones PM, Bennett MJ (2017) Chapter 4 - Disorders of mitochondrial fatty acid β-oxidation. Elsevier In: Garg U, Smith LD , eds. Biomarkers in inborn errors of metabolism. Clinical aspects and laboratory determination:87-101. - [[Jones 2017 Elsevier |»Bioblast link«]]
<br>


:::::: [[File:DeBerardinis, Chandel 2016 CORRECTION.png|600px|link=DeBerardinis 2016 Sci Adv]]
:::::: [[File:Wang 2017 Am J Reprod Immunol CORRECTION.png|400px|link=Wang 2017 Am J Reprod Immunol]]
:::: Ref. [25] DeBerardinis RJ, Chandel NS (2016) Fundamentals of cancer metabolism. Sci Adv 2:e1600200. - [[DeBerardinis 2016 Sci Adv |»Bioblast link«]]
:::: '''#21''' Wang T, Zhang M, Jiang Z, Seli E (2017) Mitochondrial dysfunction and ovarian aging. '''Am J Reprod Immunol''' 77. - [[Wang 2017 Am J Reprod Immunol |»Bioblast link«]]
<br>


:::::: [[File:Nsiah-Sefaa 2016 Bioscie Reports CORRECTION.png|600px|link=Nsiah-Sefaa 2016 Biosci Rep]]
:::: Ref. [26] Nsiah-Sefaa A, McKenzie M (2016) Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease. Biosci Rep 36:e00313. - [[Nsiah-Sefaa 2016 Biosci Rep |»Bioblast link«]]
<br>
:::::: [[File:Prochaska 2013 Springer CORRECTION.png|400px|link=Prochaska 2013 Springer]]
:::: Ref. [27] Prochaska LJ, Cvetkov TL (2013) Mitochondrial electron transport. In: Roberts, G.C.K. (eds) Encyclopedia of Biophysics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16712-6_25 - [[Prochaska 2013 Springer |»Bioblast link«]]
<br>


:::::: [[File:Fisher-Wellman 2012 Trends Endocrinol Metab CORRECTION.png|400px|link=Fisher-Wellman 2012 Trends Endocrinol Metab]] [[File:Fisher-Wellman 2012 Trends Endocrinol Metab Fig2 CORRECTION.png|400px|link=Fisher-Wellman 2012 Trends Endocrinol Metab]]
:::::: [[File:Wider 2023 Crit Care CORRECTION.png|400px|link=Wider 2023 Crit Care]]
:::: Ref. [28] Fisher-Wellman KH, Neufer PD (2012) Linking mitochondrial bioenergetics to insulin resistance via redox biology. Trends Endocrinol Metab 23:142-53. - [[Fisher-Wellman 2012 Trends Endocrinol Metab |»Bioblast link«]]
:::: '''#22''' Wider JM, Gruley E, Morse PT, Wan J, Lee I, Anzell AR, Fogo GM, Mathieu J, Hish G, O’Neil B, Neumar RW, Przyklenk K, Hüttemann M, Sanderson TH (2023) Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest. '''Crit Care''' 27:491. - [[Wider 2023 Crit Care |»Bioblast link«]]
<br>


:::::: [[File:Benard 2011 Springer CORRECTION.png|500px|link=Benard 2011 Springer]]
:::: Ref. [29] Benard G, Bellance N, Jose C, Rossignol R (2011) Relationships between mitochondrial dynamics and bioenergetics. In: Lu Bingwei (ed) Mitochondrial dynamics and neurodegeneration. Springer ISBN 978-94-007-1290-4:47-68. - [[Benard 2011 Springer |»Bioblast link«]]
<br>


:::::: [[File:Nussbaum 2005 J Clin Invest CORRECTION.png|500px|link=Nussbaum 2005 J Clin Invest]]
:::::: [[File:Wu 2022 Front Chem CORRECTION.png|400px|link=Wu 2022 Front Chem]]
:::: Ref. [30] Nussbaum RL (2005) Mining yeast in silico unearths a golden nugget for mitochondrial biology. J Clin Invest 115:2689-91. - [[Nussbaum 2005 J Clin Invest |»Bioblast link«]]
:::: '''#23''' Wu Y, Liu X, Wang Q, Han D, Lin S (2022) Fe3O4-fused magnetic air stone prepared from wasted iron slag enhances denitrification in a biofilm reactor by increasing electron transfer flow. '''Front Chem''' 10:948453. - [[Wu 2022 Front Chem |»Bioblast link«]]
<br>


:::::: [[File:Sanchez et al 2001 CORRECTION.png|600px|link=Sanchez 2001 Br J Pharmacol]]
:::: Ref. [31] Sanchez H, Zoll J, Bigard X, Veksler V, Mettauer B, Lampert E, Lonsdorfer J, Ventura-Clapier R (2001) Effect of cyclosporin A and its vehicle on cardiac and skeletal muscle mitochondria: relationship to efficacy of the respiratory chain. Br J Pharmacol 133:781-8. - [[Sanchez 2001 Br J Pharmacol |»Bioblast link«]]
<br>


:::::: [[File:Himms-Hagen, Harper 2001 CORRECTION.png|250px|link=Himms-Hagen 2001 Exp Biol Med (Maywood)]]
:::::: [[File:Zapico 2013 Aging Dis CORRECTION.png|400px|link=Zapico 2013 Aging Dis]]
:::: Ref. [32] Himms-Hagen J, Harper ME (2001) Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: an hypothesis. Exp Biol Med (Maywood) 226:78-84. - [[Himms-Hagen 2001 Exp Biol Med (Maywood) |»Bioblast link«]]
:::: '''#24''' Zapico SC, Ubelaker DH (2013) mtDNA mutations and their role in aging, diseases and forensic sciences. '''Aging Dis''' 4:364-80. - [[Zapico 2013 Aging Dis |»Bioblast link«]]
<br>


:::::: [[File:Brownlee 2001 Nature CORRECTION.png|400px|link=Brownlee 2001 Nature]]
:::: Ref. [33] Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 14:813-20. - [[Brownlee 2001 Nature |»Bioblast link«]]
:::: Ref. [34] Arden GB, Ramsey DJ (2015) Diabetic retinopathy and a novel treatment based on the biophysics of rod photoreceptors and dark adaptation. Webvision In: Kolb H, Fernandez E, Nelson R, eds. Webvision: The organization of the retina and visual system [Internet]. Salt Lake City (UT): University of Utah Health Sciences Center; 1995-. - [[Arden 2015 Webvision |»Bioblast link«]]
<br>


=== FADH<sub>2</sub>→CII misconceptions: Websites ===
== Supplement: FADH<sub>2</sub> or FADH as substrate of CII in websites ==


:::: The following graphs show zooms into the CII-related sections of figures found on the websites cited below. Erroneous presentations are marked by symbols.  
:::: Complex II ambiguities in graphical representations on FADH<sub>2</sub> as a substrate of Complex II in the canonical forward electron transfer. FADH → FAD+H ('''g'''), FADH<sub>2</sub> → FAD+2H<sup>+</sup> ('''a’''', '''c''', '''h-n'''), and FADH<sub>2</sub> → FAD ('''a''', '''b''', '''d-f''', '''o-θ''') should be corrected to FADH<sub>2</sub> → FAD (Eq. 3b). NADH → 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 → NAD<sup>+</sup>+H<sup>+</sup> ('''a-g''', '''m'''), NADH → NAD<sup>+</sup>+2H<sup>+</sup> ('''h-l'''), NADH+H<sup>+</sup> → NAD<sup>+</sup>+2H<sup>+</sup> ('''j''', '''k'''), and NADH → NAD ('''ι''') should be corrected to NADH+H<sup>+</sup> → NAD<sup>+</sup> (Eq. 3a). (Retrieved 2023-03-21 to 2023-05-04).


:::::: [[File:OpenStax Biology.png|400px]]
:::::: [[File:OpenStax Biology.png|400px]]
:::: '''Website 1''': [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.
::: ('''a''')
:::: '''Website 2''': [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 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 3''': [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] - Figure 7.11.1
:::: '''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 4''': [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 1
:::: '''Website 3''' ('''a''','''b'''): [https://www.pharmaguideline.com/2022/01/electron-transport-chain.html Pharmaguideline]
:::: '''Website 5''': [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:Khan Academy modified from OpenStax CORRECTION.png|300px]]
:::::: [[File:Khan Academy modified from OpenStax CORRECTION.png|400px]]
:::: '''Website 6''': [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.''"
::: ('''a’''')
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
:::: '''Website 9''' ('''a’''','''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''' ('''a’''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]


:::::: [[File:Jack Westin CORRECTION.png|400px]]
:::::: [[File:Expii OpenStax CORRECTION.png|400px]]
:::: '''Website 8''': [https://jackwestin.com/resources/mcat-content/oxidative-phosphorylation/electron-transfer-in-mitochondria Jack Westin MCAT Courses]
::: ('''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''' ('''a’''','''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''' ('''a’''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''β'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax


:::::: [[File:Expii OpenStax CORRECTION.png|300px]]
:::::: [[File:Biologydictionary.net CORRECTION.png|400px]]
:::: '''Website 1''': [https://openstax.org/books/biology/pages/7-4-oxidative-phosphorylation OpenStax Biology] - Fig. 7.12
::: ('''c''')
:::: '''Website 6''': [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 11''' ('''b''','''c''','''n''','''w''','''β'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
:::: '''Website 12''' ('''c''','''t'''): [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo] - extender01 / iStock / Getty Images Plus
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
:::: '''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:Labxchange CORRECTION.png|400px]]
:::::: [[File:Labxchange CORRECTION.png|400px]]
:::: '''Website 10''': [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
::: ('''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: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:Biologydictionary.net CORRECTION.png|400px]]
:::::: [[File:Videodelivery CORRECTION.png|400px]]
:::: '''Website 4''': [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 3
::: ('''f''')
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - By OpenStax College CC BY 3.0, via Wikimedia Commons
:::: '''Website 20''' ('''f'''): [https://videodelivery.net/79e91c40bf96f9692560fa378c5086b6/thumbnails/thumbnail.jpg videodelivery]
:::: '''Website 11''': [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 12''': [https://biologydictionary.net/electron-transport-chain-and-oxidative-phosphorylation/ biologydictionary.net 2018-08-21]
:::::: [[File:SparkNotes CORRECTION.png|400px]]
:::: '''Website 13''': [https://www.quora.com/Why-does-FADH2-form-2-ATP Quora]
::: ('''g''')
:::: '''Website 14''': [https://teachmephysiology.com/biochemistry/atp-production/electron-transport-chain/ TeachMePhysiology] - Fig. 1. 2023-03-13
:::: '''Website 21''' ('''g'''): [https://www.sparknotes.com/biology/cellrespiration/oxidativephosphorylation/section2/ - SparkNotes]
:::: '''Website 15''': [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo]
:::: '''Website 16''': [https://www.toppr.com/ask/question/short-long-answer-types-whatis-the-electron-transport-system-and-what-are-its-functions/ toppr]


:::::: [[File:Researchtweet CORRECTION.png|400px]]
:::::: [[File:Researchtweet CORRECTION.png|400px]]
:::: '''Website 17''': [https://researchtweet.com/mitochondrial-electron-transport-chain-2/ researchtweet]
::: ('''h''')
:::: '''Website 18''': [https://microbenotes.com/electron-transport-chain/ Microbe Notes]
:::: '''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:BiochemDen CORRECTION.png|400px]]
:::::: [[File:FlexBooks 2 0 CORRECTION.png|400px]]
:::: '''Website 19''': [https://biochemden.com/electron-transport-chain-mechanism/ BiochemDen.com]
::: ('''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:Labster Theory CORRECTION.png|400px]]
::: ('''j''')
:::: '''Website 25''' ('''j'''): [https://theory.labster.com/Electron_Transport_Chain/ Labster Theory]
 
:::::: [[File:Nau.edu CORRECTION.png|400px]]
::: ('''k''')
:::: '''Website 26''' ('''k'''): [https://www2.nau.edu/~fpm/bio205/u4fg36.html nau.edu]
 
:::::: [[File:ScienceFacts CORRECTION.png|400px]]
::: ('''l''')
:::: '''Website 27''' ('''l'''): [https://www.sciencefacts.net/electron-transport-chain.html ScienceFacts]
 
:::::: [[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''','''β'''): [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:Vector Mine CORRECTION.png|400px]]
:::::: [[File:Vector Mine CORRECTION.png|400px]]
:::: '''Website 20''': [https://www.dreamstime.com/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram-electron-transport-chain-as-respiratory-embedded-image235345232 dreamstime]
::: ('''p''')
:::: '''Website 21''': [https://vectormine.com/item/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram/ VectorMine]
:::: '''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]


:::::: [[File:Creative-biolabs CORRECTION.png|400px]]
:::::: [[File:YouTube Dirty Medicine Biochemistry CORRECTION.png|400px]]
:::: '''Website 22''': [https://www.creative-biolabs.com/drug-discovery/therapeutics/electron-transport-chain.htm creative-biolabs]
::: ('''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


:::::: [[File:Khan Academy CORRECTION.png|400px]]
:::::: [[File:DBriers CORRECTION.png|400px]]
:::: '''Website 6''': [https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc Khan Academy]
::: ('''r''')
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
:::: '''Website 34''' ('''r'''): [http://www.dbriers.com/tutorials/ DBriers]


:::::: [[File:Expii-Whitney, Rolfes 2002 CORRECTION.png|400px]]
:::::: [[File:SNC1D CORRECTION.png|400px]]
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Whitney, Rolfes 2002
::: ('''s''')
:::: '''Website 35''' ('''s'''): [https://sbi4uraft2014.weebly.com/electron-transport-chain.html SNC1D - BIOLOGY LESSON PLAN BLOG]


:::::: [[File:FlexBooks 2 0 CORRECTION.png|400px]]
:::::: [[File:ThoughtCo-Getty Images CORRECTION.png|400px]]
:::: '''Website 23''': [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
::: ('''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:Hyperphysics CORRECTION.png|400px]]
:::::: [[File:Hyperphysics CORRECTION.png|400px]]
:::: '''Website 24''': [http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/Complex1.html hyperphysics]
::: ('''u''')
:::: '''Website 37''' ('''u'''): [http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/Complex1.html hyperphysics]
 
:::::: [[File:Khan Academy CORRECTION.png|400px]]
::: ('''v''')
:::: '''Website 9''' ('''a’''','''b''','''v'''): [https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc Khan Academy]
:::: '''Website 10''' ('''a’''','''b''','''v'''): [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]


:::::: [[File:Labster Theory CORRECTION.png|400px]]
:::::: [[File:Expii-Whitney, Rolfes 2002 CORRECTION.png|400px]]
:::: '''Website 25''': [https://theory.labster.com/Electron_Transport_Chain/ Labster Theory]
::: ('''w''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''β'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Whitney, Rolfes 2002


:::::: [[File:Nau.edu CORRECTION.png|400px]]
:::::: [[File:UrbanPro CORRECTION.png|400px]]
:::: '''Website 26''': [https://www2.nau.edu/~fpm/bio205/u4fg36.html nau.edu]
::: ('''x''')
:::: '''Website 38''' ('''x'''): [https://www.urbanpro.com/ba-tuition/oxidative-phosphorylation UrbanPro]


:::::: [[File:Quizlet CORRECTION.png|400px]]
:::::: [[File:Quizlet CORRECTION.png|400px]]
:::: '''Website 27''': [https://quizlet.com/245664214/electron-transport-chain-facts-of-cell-respiration-diagram/ Quizlet]
::: ('''y''')
:::: '''Website 39''' ('''y'''): [https://quizlet.com/245664214/electron-transport-chain-facts-of-cell-respiration-diagram/ Quizlet]


:::::: [[File:ScienceDirect CORRECTION.png|400px]]
:::::: [[File:Unm.edu CORRECTION.png|400px]]
:::: '''Website 28''': [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]
::: ('''z''')
:::: '''Website 40''' ('''z'''): [https://www.unm.edu/~lkravitz/Exercise%20Phys/ETCstory.html unm.edu]
 
:::::: [[File:YouTube sciencemusicvideos CORRECTION.png|400px]]
::: ('''α''')
:::: '''Website 41''' ('''α'''): [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:Expii-Gabi Slizewska CORRECTION.png|400px]]
::: ('''β''')
:::: '''Website 11''' ('''b''','''c''','''n''','''w''','''β'''): [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii expii] - Image source: By Gabi Slizewska


:::::: [[File:ScienceFacts CORRECTION.png|400px]]
:::::: [[File:BiochemDen CORRECTION.png|400px]]
:::: '''Website 29''': [https://www.sciencefacts.net/electron-transport-chain.html ScienceFacts]
::: ('''γ''')
:::: '''Website 42''' ('''γ'''): [https://biochemden.com/electron-transport-chain-mechanism/ BiochemDen.com]


:::::: [[File:SNC1D CORRECTION.png|400px]]
:::::: [[File:Hopes CORRECTION.png|400px]]
:::: '''Website 30''': [https://sbi4uraft2014.weebly.com/electron-transport-chain.html SNC1D - BIOLOGY LESSON PLAN BLOG]
:::('''δ''')
:::: '''Website 43''' ('''δ'''): [https://hopes.stanford.edu/riboflavin/ hopes, Huntington’s outreach project for education, at Stanford]


:::::: [[File:Unm.edu CORRECTION.png|400px]]
:::::: [[File:Studocu CORRECTION.png|400px]]
:::: '''Website 31''': [https://www.unm.edu/~lkravitz/Exercise%20Phys/ETCstory.html unm.edu]
::: ('''ε''')
:::: '''Website 44''' ('''ε'''): [ https://www.studocu.com/en-gb/document/university-college-london/mammalian-physiology/electron-transport-chain/38063777 studocu, University College London]


:::::: [[File:Wikimedia ETC CORRECTION.png|400px]]
:::::: [[File:ScienceDirect CORRECTION.png|400px]]
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - By User:Rozzychan CC BY-SA 2.5, via Wikimedia Commons
::: ('''ζ''')
:::: '''Website 32''': [https://commons.wikimedia.org/wiki/File:Mitochondrial_electron_transport_chain.png Wikimedia]
:::: '''Website 45''' ('''ζ'''): [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:YouTube Dirty Medicine Biochemistry CORRECTION.png|400px]]
:::::: [[File:BBC BITESIZE CORRECTION.png|400px]]
:::: '''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
::: ('''η''')
:::: '''Website 46''' ('''η'''): [https://www.bbc.co.uk/bitesize/guides/zdq9382/revision/5 BBC BITESIZE cK-12]


:::::: [[File:YouTube sciencemusicvideos CORRECTION.png|400px]]
:::::: [[File:Freepik CORRECTION.png|400px]]
:::: '''Website 34''': [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
::: ('''θ''')
:::: '''Website 47''' ('''θ'''): [https://www.freepik.com/premium-vector/oxidative-phosphorylation-process-electron-transport-chain-final-step-cellular-respiration_29211885.htm freepik]


:::::: [[File:ThoughtCo-Getty Images CORRECTION.png|400px]]
:::::: [[File:LibreTexts Chemistry_CORRECTION.png|400px]]
:::: '''Website 15''': [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo] - extender01 / iStock / Getty Images Plus
::: ('''ι''')
:::: '''Website 17''': [https://www.dreamstime.com/royalty-free-stock-photography-electron-transport-chain-illustration-oxidative-phosphorylation-image36048617 dreamstime]
:::: '''Website 48''' ('''ι'''): [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 – Fig. 12.4.3


:::::: [[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>


== CII and fatty acid oxidation ==


:::::::: [[File:SUIT-catg F.jpg|300px|F-junction|link=Fatty acid oxidation pathway control state]]  [[File:Wang 2019 Fig8.png|300px|link=Wang Y 2019 J Biol Chem]]
<big>'''from FAO and CII ambiguitiy to CII as a H<sup>+</sup> in websites'''</big>
:::: Fatty acid oxidation requires electron transferring flavoprotein CETF and CI for electron entry into the Q-junction ([[Gnaiger_2020_BEC_MitoPathways |Gnaiger 2020]]; [[Wang Y 2019 J Biol Chem |Wang et al 2019]]; see figures on the right).


:::::: [[File:Missaglia 2021 Crit Rev Biochem Mol Biol CORRECTION.png|600px]]
:::::: [[File:CHM333 LECTURES CORRECTION.png|250px]]
:::: When FADH<sub>2</sub> is erroneously shown as a substrate of CII <span style="color:#FF0000">(1)</span>, a role of CII in fatty acid oxidation is suggested as a consequence <span style="color:#FF0000">(2)</span>.
:::: '''xx''' [https://www.chem.purdue.edu/courses/chm333/Spring%202013/Lectures/Spring%202013%20Lecture%2037%20-%2038.pdf CHM333 LECTURES 37 & 38: 4/27 – 29/13 SPRING 2013 Professor Christine Hrycyna]
<br>


:::: '''Website 35''': [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>.
(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>.


:::::: [[File:Expii-Gabi Slizewska CORRECTION.png|600px]]
:::: '''Website 50''': [https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/ The Medical Biochemistry Page]: ‘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 shuttle’ (Figure 8d).
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By Gabi Slizewska. The ambiguity in the graphical representation is solidified as an error in the text: ''In the second step, Complex II receives electrons from FADH<sub>2</sub>, oxidizing it to FAD.''


::::* "Since mitochondrial Complex II also participates in the oxidation of fatty acids (6), .." (quote from [[Lemmi 1990 Biochem Med Metab Biol |Lemmi et al 1990]]).
:::: '''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 – 29/13 SPRING 2013 Professor Christine Hrycyna]: Acyl-CoA dehydrogenase is listed under 'Electron transfer in Complex II'.
::::::* ''Ref 6'': Tzagoloff A (1982) Mitochondria. Plenum, New York.
::::::* This quote is ambiguous. The textbook by [[Tzagoloff 1982 Plenum Press |Tzagoloff (1982)]] represents fatty acid oxidation in figures and text without involvement of CII. Oxidation of acetyl-CoA, however, proceeds in the TCA cycle into which CII is integrated.


:::::: [[File:FAO-CII Medical Biochemistry Page.jpg|400px|right|link=https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/]]
:::: '''Website 36''': [https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/ The Medical Biochemistry Page] - Figure and text go together: "''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 shuttle''".


:::: '''Website 37''': [https://www.chem.purdue.edu/courses/chm333/Spring%202013/Lectures/Spring%202013%20Lecture%2037%20-%2038.pdf CHM333 LECTURES 37 & 38: 4/27 – 29/13 SPRING 2013 Professor Christine Hrycyna] - Acyl-CoA dehydrogenase is listed under 'Electron transfer in Complex II'.
:::::: [[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]: ‘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 electrons’ (retrieved 2023-05-04).


:::::: [[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
|injuries=
|enzymes=Complex II;succinate dehydrogenase
|organism=
|additional=Ambiguity crisis, FAT4BRAIN, Publication:FAT4BRAIN
|tissues=
|preparations=
|topics=
|instruments=
|additional=MitoPedia:FAT4BRAIN
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}}

Latest revision as of 08:48, 1 May 2024

Publications in the MiPMap
Gnaiger E (2023) Complex II ambiguities ― 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)

» MitoFit Preprints 2023.3.v6.

MitoFit pdf

Complex II ambiguities ― FADH2 in the electron transfer system

Gnaiger Erich (2023) MitoFit Prep

Abstract:

CII-ambiguities Graphical abstract.png
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
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 - »Link to all versions«

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 β-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.
• 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

• O2k-Network Lab: AT Innsbruck Oroboros

» 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 Union’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
Bektas 2019 Aging (Albany NY) CORRECTION.png
#1 Bektas A, Schurman SH, Gonzalez-Freire M, Dunn CA, Singh AK, Macian F, Cuervo AM, Sen R, Ferrucci L (2019) Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy. Aging (Albany NY) 11:9234-63. - »Bioblast link«


Ben-Shachar 2009 J Neural Transm (Vienna) CORRECTION.png
#2 Ben-Shachar D (2009) The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia. J Neural Transm (Vienna) 116:1383-96. - »Bioblast link«


Bon 2022 J Clin Case Rep Stud CORRECTION.png
#3 Bon E, Maksimovich NY, Dremza IK (2022) Alendronate-induced nephropathy. J Clin Case Rep Stud 3. - »Bioblast link«


Elsaeed 2021 Medicine Updates CORRECTION.png
#4 Elsaeed EM, Hamad A, Erfan OS, Elshahat M, Ebrahim F (2021) Role played by hippocampal apoptosis, autophagy and necroptosis in pathogenesis of diabetic cognitive dysfunction: a review of literature. Medicine Updates 6:41-63. - »Bioblast link«


Facucho-Oliveira 2009 Stem Cell Rev Rep CORRECTION.png
#5 Facucho-Oliveira JM, St John JC (2009) The relationship between pluripotency and mitochondrial DNA proliferation during early embryo development and embryonic stem cell differentiation. Stem Cell Rev Rep 5:140-58. - »Bioblast link«


Iqbal 2014 Springer, New York CORRECTION.png
#6 Iqbal T, Welsby PJ, Howarth FC, Bidasee K, Adeghate E, Singh J (2014) Effects of diabetes-induced hyperglycemia in the heart: biochemical and structural slterations. In: Turan B, Dhalla N (eds) Diabetic cardiomyopathy. Advances in biochemistry in health and disease 9. Springer, New York. - »Bioblast link«


Keogh 2015 Biochim Biophys Acta CORRECTION.png
#7 Keogh MJ, Chinnery PF (2015) Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta 1847:1401-11. - »Bioblast link«


Kunst 2023 Biomedicines CORRECTION.png
#8 Kunst C, Schmid S, Michalski M, Tümen D, Buttenschön J, Müller M, Gülow K (2023) The influence of gut microbiota on oxidative stress and the immune system. Biomedicines 11:1388. - »Bioblast link«


Lal 2018 Springer CORRECTION.png
#9 Lal MA (2018) Respiration. In: Bhatla SC, Lal MA (eds) Plant physiology, development and metabolism. Springer, Singapore:253-314. - »Bioblast link«


Lane 2000 Pediatr Res CORRECTION.png
#10 Lane RH, Tsirka AE, Gruetzmacher EM (2000) Uteroplacental insufficiency alters cerebral mitochondrial gene expression and DNA in fetal and juvenile rats. Pediatr Res 47:792-7. - »Bioblast link«


Palma 2023 Oncogene CORRECTION.png
#11 Palma FR, Gantner BN, Sakiyama MJ, Kayzuka C, Shukla S, Lacchini R, Cunniff B, Bonini MG (2023) ROS production by mitochondria: function or dysfunction? Oncogene. - »Bioblast link«


Quintard 2018 Springer, Cham CORRECTION.png
#12 Quintard H, Fontaine E, Ichai C (2018) Energy metabolism: from the organ to the cell. In: Ichai, C., Quintard, H., Orban, JC. (eds) Metabolic Disorders and Critically Ill Patients. Springer, Cham. - »Bioblast link«


Reiss 2022 Exp Gerontol CORRECTION.png
#13 Reiss AB, Ahmed S, Dayaramani C, Glass AD, Gomolin IH, Pinkhasov A, Stecker MM, Wisniewski T, De Leon J (2022) The role of mitochondrial dysfunction in Alzheimer's disease: A potential pathway to treatment. Exp Gerontol 164:111828. - »Bioblast link«


Saghiv 2020 Springer, Cham CORRECTION.png
#14 Saghiv MS, Sagiv MS (2020) Metabolism. In: Basic Exercise Physiology. Springer, Cham. - »Bioblast link«


SiouNing 2023 Molecules CORRECTION.png
#15 SiouNing AS, Seong TS, Kondo H, Bhassu S (2023) MicroRNA regulation in infectious diseases and its potential as a biosensor in future aquaculture industry: a review. Molecules 28:4357. - »Bioblast link«


St John 2012 Cell Tissue Res CORRECTION.png
#16 St John JC (2012) Transmission, inheritance and replication of mitochondrial DNA in mammals: implications for reproductive processes and infertility. Cell Tissue Res 349:795-808. - »Bioblast link«


Su 2020 Mol Biol Rep CORRECTION.png
#17 Su J, Ye D, Gao C, Huang Q, Gui D (2020) Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury. Mol Biol Rep 47:8023-35. - »Bioblast link«


Thorgersen 2022 Front Microbiol CORRECTION.png
#18 Thorgersen MP, Schut GJ, Poole FL 2nd, Haja DK, Putumbaka S, Mycroft HI, de Vries WJ, Adams MWW (2022) Obligately aerobic human gut microbe expresses an oxygen resistant tungsten-containing oxidoreductase for detoxifying gut aldehydes. Front Microbiol 13:965625. - »Bioblast link«


Venkatachalam 2022 Cells CORRECTION.png
#19 Venkatachalam K (2022) Regulation of aging and longevity by ion channels and transporters. Cells 11:1180. - »Bioblast link«


Wall 2006 Am J Physiol Heart Circ Physiol CORRECTION.png
#20 Wall JA, Wei J, Ly M, Belmont P, Martindale JJ, Tran D, Sun J, Chen WJ, Yu W, Oeller P, Briggs S, Gustafsson AB, Sayen MR, Gottlieb RA, Glembotski CC (2006) Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6. Am J Physiol Heart Circ Physiol 291:H2462-72. - »Bioblast link«


Wang 2017 Am J Reprod Immunol CORRECTION.png
#21 Wang T, Zhang M, Jiang Z, Seli E (2017) Mitochondrial dysfunction and ovarian aging. Am J Reprod Immunol 77. - »Bioblast link«


Wider 2023 Crit Care CORRECTION.png
#22 Wider JM, Gruley E, Morse PT, Wan J, Lee I, Anzell AR, Fogo GM, Mathieu J, Hish G, O’Neil B, Neumar RW, Przyklenk K, Hüttemann M, Sanderson TH (2023) Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest. Crit Care 27:491. - »Bioblast link«


Wu 2022 Front Chem CORRECTION.png
#23 Wu Y, Liu X, Wang Q, Han D, Lin S (2022) Fe3O4-fused magnetic air stone prepared from wasted iron slag enhances denitrification in a biofilm reactor by increasing electron transfer flow. Front Chem 10:948453. - »Bioblast link«


Zapico 2013 Aging Dis CORRECTION.png
#24 Zapico SC, Ubelaker DH (2013) mtDNA mutations and their role in aging, diseases and forensic sciences. Aging Dis 4:364-80. - »Bioblast link«


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 → FAD+H (g), FADH2 → FAD+2H+ (a’, c, h-n), and FADH2 → FAD (a, b, d-f, o-θ) should be corrected to FADH2 → FAD (Eq. 3b). NADH → NAD+ is frequently written in graphs without showing the H+ on the left side of the arrow, except for (p-r). NADH → NAD++H+ (a-g, m), NADH → NAD++2H+ (h-l), NADH+H+ → NAD++2H+ (j, k), and NADH → NAD (ι) should be corrected to NADH+H+ → 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
(a’)
Website 9 (a’,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 (a’,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
Website 3 (a,b): Pharmaguideline
Website 4 (a,b): Texas Gateway - Figure 7.13
Website 5 (a,b): - CUNY
Website 6 (a,b): lumen Biology for Majors I - Fig. 3
Website 9 (a’,b,v): Khan Academy - Image modified from "Oxidative phosphorylation: Figure 3," by Openstax College, Biology (CC BY 3.0)
Website 10 (a’,b,v): Saylor Academy
Website 11 (b,c,n,w,β): expii - Image source: By CNX OpenStax
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Website 11 (b,c,n,w,β): expii - Image source: By CNX OpenStax
Website 12 (c,t): ThoughtCo - extender01 / iStock / Getty Images Plus
Website 13 (c): wikimedia 30148497 - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, 2013-06-19
Website 14 (c): biologydictionary.net 2018-08-21
Website 15 (c): Quora
Website 16 (c): TeachMePhysiology - Fig. 1. 2023-03-13
Website 17 (c): toppr
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Website 18 (d): Labxchange - Figure 8.15 credit: modification of work by Klaus Hoffmeier
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Website 19 (e): Jack Westin MCAT Courses
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Website 20 (f): videodelivery
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Website 21 (g): - SparkNotes
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Website 22 (h,t): researchtweet
Website 23 (h): Microbe Notes
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Website 24 (i): FlexBooks - CK-12 Biology for High School- 2.28 Electron Transport, Figure 2
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Website 25 (j): Labster Theory
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Website 26 (k): nau.edu
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Website 27 (l): ScienceFacts
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Website 28 (m): cK-12
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Website 11 (b,c,n,w,β): expii - Image source: By CNX OpenStax
Website 29 (n): Wikimedia
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Website 30 (o): creative-biolabs
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Website 31 (p): dreamstime
Website 32 (p): VectorMine
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Website 33: YouTube Dirty Medicine Biochemistry - Uploaded 2019-07-18
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Website 34 (r): DBriers
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Website 35 (s): SNC1D - BIOLOGY LESSON PLAN BLOG
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Website 12 (c,t): ThoughtCo - extender01 / iStock / Getty Images Plus
Website 22 (h,t): researchtweet
Website 36 (t): dreamstime
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Website 37 (u): hyperphysics
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Website 9 (a’,b,v): Khan Academy
Website 10 (a’,b,v): Saylor Academy
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Website 11 (b,c,n,w,β): expii - Whitney, Rolfes 2002
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Website 38 (x): UrbanPro
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Website 39 (y): Quizlet
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Website 40 (z): unm.edu
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Website 41 (α): YouTube sciencemusicvideos - Uploaded 2014-08-19
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Website 42 (γ): BiochemDen.com
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Website 43 (δ): hopes, Huntington’s outreach project for education, at Stanford
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Website 44 (ε): [ https://www.studocu.com/en-gb/document/university-college-london/mammalian-physiology/electron-transport-chain/38063777 studocu, University College London]
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Website 45 (ζ): ScienceDirect
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Website 46 (η): BBC BITESIZE cK-12
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Website 47 (θ): freepik
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Website 48 (ι): - LibreTexts Chemistry - The Citric Acid Cycle and Electron Transport – 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 – 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: ‘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 shuttle’ (Figure 8d).
Website 51: CHM333 LECTURES 37 & 38: 4/27 – 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: ‘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 electrons’ (retrieved 2023-05-04).
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xx: BioNinja (retrieved 2023-05-04).


Questions.jpg


Click to expand or collaps
Bioblast links: Substrates and cofactors - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
Substrate
» Substrate
» Product
» Substrates as electron donors
» Cellular substrates
» MitoPedia: Substrates and metabolites
» Substrate-uncoupler-inhibitor titration
Cofactor
» Cofactor
» Coenzyme, cosubstrate
» Nicotinamide adenine dinucleotide
» Coenzyme Q2
» Prosthetic group
» Flavin adenine dinucleotide
Referennces
» Gnaiger E (2023) Complex II ambiguities ― 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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