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Difference between revisions of "Complex II ambiguities"

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{{MitoPedia
{{MitoPedia
|abbr=CII ambiguities
|abbr=CII ambiguities
|description=Two ambiguities or misconceptions around respiratory Complex II (CII) have their roots in the narrative that reduced coenzymes (NADH and FADH<sub>2</sub>) feed electrons from the tricarboxylic acid (TCA) cycle into the mitochondrial electron transfer system. In graphical representations propagating the first ambiguity, succinate dehydrogenase or CII in the canonical (forward) TCA cycle is shown to reduce FAD to FADH<sub>2</sub> (correct), yet CII in the membrane-bound electron transfer system (ETS) is paradoxically represented as the site of oxidation of FADH<sub>2</sub> to FAD. With minor expansion of the tale on electron transfer from FADH<sub>2</sub> into CII, we arrive at the misconception that FADH<sub>2</sub> generated by electron transferring flavoprotein (CETF) in fatty acid oxidation and by mitochondrial glycerophosphate dehydrogenase (CGpDH) feeds electrons into the ETS through CII. For clarification, recall that NADH and succinate formed in the TCA cycle in the mitochondrial matrix are the upstream substrates of Complexes CI and CII, whereas the reduced flavin groups FMNH<sub>2</sub> of flavin mononucleotide and FADH<sub>2</sub> of flavin adenine dinucleotide are products of CI and CII, respectively, with downstream electron flow from CI and CII into the [[Q-junction]]. CETF and CGpDH feed electrons into the Q-junction convergent with  but not through CII into the Q-junction. Numerous Complex II ambiguities in the literature with discrepancies in graphical representations and text require quality control to secure scientific standards in current communications on bioenergetics.
|description=[[File:CII-ambiguities Graphical abstract.png|300px|left|link=Gnaiger 2023 MitoFit CII]]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.
|info=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
}}
}}
'''» ''Links:''''' [[Ambiguity crisis]], [[:Category:Ambiguity crisis - NAD and H+ |Complex I and hydrogen ion ambiguities in the electron transfer system]]
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Communicated by [[Gnaiger E]] (2023-03-03) last update 2023-03-21
== A game of cards ==
== 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>


:::: 33 copies or variations of a CII ambiguity theme


== FADH<sub>2</sub> and FMNH<sub>2</sub> in the S- and N-pathways ==
:::::: [[File:Martell 2023 Nat Commun CORRECTION.png|400px|link=Martell 2023 Nat Commun]]
[[File:N-S FADH2-FMNH2.png|right|400px]]
:::: '''1.''' Martell E, Kuzmychova H, Kaul E, Senthil H, Chowdhury SR, Morrison LC, Fresnoza A, Zagozewski J, Venugopal C, Anderson CM, Singh SK, Banerji V, Werbowetski-Ogilvie TE, Sharif T (2023) Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma. '''Nat Commun''' 14:2502. - [[Martell 2023 Nat Commun |»Bioblast link«]]
:::: 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]]).
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:::: 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:Solhaug 2023 Cytotechnology CORRECTION.png|400px|link=Solhaug 2023 Cytotechnology]]
:::: '''2.''' Solhaug A, Gjessing M, Sandvik M, Eriksen GS (2023) The gill epithelial cell lines RTgill-W1, from Rainbow trout and ASG-10, from Atlantic salmon, exert different toxicity profiles towards rotenone. '''Cytotechnology''' 75:63-75. - [[Solhaug 2023 Cytotechnology |»Bioblast link«]]
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:::: 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
:::::: [[File:Fahimi 2022 Trends in Chemistry CORRECTION.png|400px|link=Fahimi 2022 Trends in Chemistry]]
:::: Ref. [3]  Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. https://doi.org/10.26124/bec:2020-0001.v1
:::: '''3.''' Fahimi P, Matta CF (2022) The hot mitochondrion paradox: reconciling theory and experiment. '''Trends in Chemistry''' 4:4-20. - [[Fahimi 2022 Trends in Chemistry |»Bioblast link«]]
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:::::: [[File:Foo 2022 Trends Microbiol CORRECTION.png|400px|link=Foo 2022 Trends Microbiol]]
:::: '''4.''' Foo J, Bellot G, Pervaiz S, Alonso S (2022) Mitochondria-mediated oxidative stress during viral infection. '''Trends Microbiol''' 30:679-92. - [[Foo 2022 Trends Microbiol |»Bioblast link«]]
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=== The source and consequence of Complex II ambiguities ===
:::::: [[File:Joshi 2022 Biomolecules CORRECTION.png|400px|link=Joshi 2022 Biomolecules]]
:::: '''5.''' Joshi A, Ito T, Picard D, Neckers L (2022) The mitochondrial HSP90 paralog TRAP1: structural dynamics, interactome, role in metabolic regulation, and inhibitors. '''Biomolecules''' 12:880. - [[Joshi 2022 Biomolecules |»Bioblast link«]]
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:::: 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:Manickam 2022 J Control Release CORRECTION.png|400px|link=Manickam 2022 J Control Release]]
 
:::: '''6.''' Manickam DS (2022) Delivery of mitochondria via extracellular vesicles - a new horizon in drug delivery. '''J Control Release''' 343:400-7. - [[Manickam 2022 J Control Release |»Bioblast link«]]
:::::: [[File:Cooper 2000 Sunderland 10-9.png|700px]]
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:::: 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.'
:::::: ''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).
 
:::: (''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 ===
 
:::: 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
::::'''(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);
::::'''(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]]
:::::: [[File:Wu 2022 Neuromolecular Med CORRECTION.png|400px|link=Wu 2022 Neuromolecular Med]]
:::: 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«]]
:::: '''7.''' Wu Z, Ho WS, Lu R (2022) Targeting mitochondrial oxidative phosphorylation in glioblastoma therapy. '''Neuromolecular Med''' 24:18-22. - [[Wu 2022 Neuromolecular Med |»Bioblast link«]]
<br>
<br>


:::::: [[File:Chen 2022 Am J Physiol Cell Physiol CORRECTION.png|500px|link=Chen 2022 Am J Physiol Cell Physiol]]
:::::: [[File:Yang 2022 J Cleaner Production CORRECTION.png|400px|link=Yang 2022 J Cleaner Production]]
:::: 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«]]
:::: '''8.''' Yang Y, Zhang X, Hu X, Zhao J, Chen X, Wei X, Yu X (2022) Analysis of the differential metabolic pathway of cultured ''Chlorococcum humicola'' with hydroquinone toxic sludge extract. '''J Cleaner Production''' 370:133486. - [[Yang 2022 J Cleaner Production |»Bioblast link«]]
<br>
<br>


:::::: [[File:Turton 2022 Int J Mol Sci CORRECTION.png|500px|link=Turton 2022 Int J Mol Sci]]
:::::: [[File:Ignatieva 2021 Int J Mol Sci CORRECTION.png|400px|link=Ignatieva 2021 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«]]
:::: '''9.''' Ignatieva E, Smolina N, Kostareva A, Dmitrieva R (2021) Skeletal muscle mitochondria dysfunction in genetic neuromuscular disorders with cardiac phenotype. '''Int J Mol Sci''' 22:7349. - [[Ignatieva 2021 Int J Mol Sci |»Bioblast link«]]
<br>
<br>


:::::: [[File:Ahmad 2022 StatPearls CORRECTION.png|400px|link=Ahmad 2022 StatPearls Publishing]]
:::::: [[File:Anoar 2021 Front Neurosci CORRECTION.jpg|400px|link=Anoar 2021 Front Neurosci]]
:::: 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«]]
:::: '''10.''' Anoar S, Woodling NS, Niccoli T (2021) Mitochondria dysfunction in frontotemporal dementia/amyotrophic lateral sclerosis: lessons from ''Drosophila'' models. '''Front Neurosci''' 15:786076. - [[Anoar 2021 Front Neurosci |»Bioblast link«]]
<br>
<br>


:::::: [[File:Yuan 2022 Oxid Med Cell Longev CORRECTION.png|500px|link=Yuan 2022 Oxid Med Cell Longev]]
:::::: [[File:Shields 2021 Front Cell Dev Biol CORRECTION.png|400px|link=Shields 2021 Front Cell Dev Biol]]
:::: 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«]]
:::: '''11.''' Shields HJ, Traa A, Van Raamsdonk JM (2021) Beneficial and detrimental effects of reactive oxygen species on lifespan: a comprehensive review of comparative and experimental studies. '''Front Cell Dev Biol''' 9:628157. - [[Shields 2021 Front Cell Dev Biol |»Bioblast link«]]
<br>
<br>


:::: [[File:Chandel 2021 Cold Spring Harb Perspect Biol CORRECTION.png|1000px|link=Chandel 2021 Cold Spring Harb Perspect Biol]]  
:::::: [[File:Vesga 2021 Med Chem Res CORRECTION.png|400px|link=Vesga 2021 Med Chem Res]]
:::: Ref. [9] Chandel NS (2021) Mitochondria. Cold Spring Harb Perspect Biol 13:a040543. - [[Chandel 2021 Cold Spring Harb Perspect Biol |»Bioblast link«]]  
:::: '''12.''' Vesga LC, Silva AMP, Bernal CC, Mendez-Sánchez SC, Bohórquez ARR (2021) Tetrahydroquinoline/4,5-dihydroisoxazole hybrids with a remarkable effect over mitochondrial bioenergetic metabolism on melanoma cell line B16F10. '''Med Chem Res''' 30:2127–43. - [[Vesga 2021 Med Chem Res |»Bioblast link«]]
<br>
<br>


:::::: [[File:Yin 2021 FASEB J CORRECTION.png|500px|link=Yin 2021 FASEB J]]
:::::: [[File:Gopalakrishnan 2020 Sci Rep CORRECTION.png|400px|link=Gopalakrishnan 2020 Sci Rep]]
:::: 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«]]
:::: '''13.''' Gopalakrishnan S, Mehrvar S, Maleki S, Schmitt H, Summerfelt P, Dubis AM, Abroe B, Connor TB Jr, Carroll J, Huddleston W, Ranji M, Eells JT (2020) Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa. '''Sci Rep''' 10:20382. - [[Gopalakrishnan 2020 Sci Rep |»Bioblast link«]]
 
:::::: [[File:Missaglia 2021 CORRECTION.png|500px|link=Missaglia 2021 Crit Rev Biochem Mol Biol]]
:::: 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«]]  
<br>
<br>


:::::: [[File:Gasmi 2021 Arch Toxicol CORRECTION.png|500px|link=Gasmi 2021 Arch Toxicol]]
:::::: [[File:Aye 2022 Am J Obstet Gynecol CORRECTION.png|400px|link=Aye 2022 Am J Obstet Gynecol]]
:::: 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«]]
:::: '''14.''' Aye ILMH, Aiken CE, Charnock-Jones DS, Smith GCS (2022) Placental energy metabolism in health and disease-significance of development and implications for preeclampsia. '''Am J Obstet Gynecol''' 226:S928-44. - [[Aye 2022 Am J Obstet Gynecol |»Bioblast link«]]
<br>
<br>


:::::: [[File:Turton 2021 Expert Opinion Orphan Drugs CORRECTION.png|400px|link=Turton 2021 Expert Opinion Orphan Drugs]]
:::::: [[File:Lu 2023 Explor Res Hypothesis Med CORRECTION.png|400px|link=Lu 2023 Explor Res Hypothesis Med]]
:::: 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.''' Lu F (2023) Hypothetical hydrogenase activity of human mitochondrial Complex I and its role in preventing cancer transformation. '''Explor Res Hypothesis Med''' 8:280-5. - [[Lu 2023 Explor Res Hypothesis Med |»Bioblast link«]]
<br>
<br>


:::::: [[File:Martinez-Reyes, Chandel 2020 CORRECTION.png|600px|link=Martinez-Reyes 2020 Nat Commun]]
:::::: [[File:Cojocaru 2023 Antioxidants (Basel) CORRECTION.png|400px|link=Cojocaru 2023 Antioxidants (Basel)]]
:::: 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«]]
:::: '''16.''' Cojocaru KA, Luchian I, Goriuc A, Antoci LM, Ciobanu CG, Popescu R, Vlad CE, Blaj M, Foia LG (2023) Mitochondrial dysfunction, oxidative stress, and therapeutic strategies in diabetes, obesity, and cardiovascular disease. '''Antioxidants (Basel)''' 12:658. - [[Cojocaru 2023 Antioxidants (Basel) |»Bioblast link«]]
<br>
<br>


:::::: [[File:Raimondi 2020 Br J Cancer CORRECTION.png|400px|link=Raimondi 2020 Br J Cancer]]
:::::: [[File:Faria 2023 Pharmaceutics CORRECTION.png|400px|link=Faria 2023 Pharmaceutics]]
:::: 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«]]
:::: '''17.''' Faria R, Boisguérin P, Sousa Â, Costa D (2023) Delivery systems for mitochondrial gene therapy: a review. '''Pharmaceutics''' 15:572. - [[Faria 2023 Pharmaceutics |»Bioblast link«]]
<br>
<br>


:::::: [[File:Morelli 2019 Open Biol CORRECTION.png|500px|link=Morelli 2019 Open Biol]]
:::::: [[File:George 2023 Platelets CORRECTION.png|400px|link=George 2023 Platelets]]
:::: 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«]]
:::: '''18.''' George CE, Saunders CV, Morrison A, Scorer T, Jones S, Dempsey NC (2023) Cold stored platelets in the management of bleeding: is it about bioenergetics? '''Platelets''' 34:2188969 - [[George 2023 Platelets |»Bioblast link«]]
<br>
<br>


:::::: [[File:Lewis 2019 CORRECTION.png|500px|link=Lewis 2019 Int J Mol Sci]]
:::::: [[File:Narine 2022 Front Cell Neurosci CORRECTION.png|400px|link=Narine 2022 Front Cell Neurosci]]
:::: 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«]]
:::: '''19.''' Narine M, Colognato H (2022) Current insights into oligodendrocyte metabolism and its power to sculpt the myelin landscape. '''Front Cell Neurosci''' 16:892968. - [[Narine 2022 Front Cell Neurosci |»Bioblast link«]]
<br>
<br>


:::::: [[File:Sarmah 2019 Transl Stroke Res CORRECTION.png|500px|link=Sarmah 2019 Transl Stroke Res]]
:::::: [[File:Sainero-Alcolado 2022 Cell Death Differ CORRECTION.png|400px|link=Sainero-Alcolado 2022 Cell Death Differ]]
:::: 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«]]
:::: '''20.''' Sainero-Alcolado L, Liaño-Pons J, Ruiz-Pérez MV, Arsenian-Henriksson M (2022) Targeting mitochondrial metabolism for precision medicine in cancer. '''Cell Death Differ''' 29:1304-17. - [[Sainero-Alcolado 2022 Cell Death Differ |»Bioblast link«]]
 
:::::: [[File:Yepez 2018 PLOS One Fig1B.jpg|300px|link=Yepez 2018 PLOS One]]
:::: 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«]]
<br>
<br>


:::::: [[File:Chowdhury 2018 Oxid Med Cell Longev CORRECTION.png|400px|link=Chowdhury 2018 Oxid Med Cell Longev]]
:::::: [[File:Nguyen 2021 Brief Bioinform CORRECTION.png|400px|link=Nguyen 2021 Brief Bioinform]]
:::: 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«]]
:::: '''21.''' Nguyen TT, Nguyen DK, Ou YY (2021) Addressing data imbalance problems in ligand-binding site prediction using a variational autoencoder and a convolutional neural network. '''Brief Bioinform''' 22:bbab277. - [[Nguyen 2021 Brief Bioinform |»Bioblast link«]]
<br>
<br>


:::::: [[File:De Villiers 2018 Adv Exp Med Biol CORRECTION.png|400px|link=De Villiers 2018 Adv Exp Med Biol]]
:::::: [[File:Prasuhn 2021 Front Cell Dev Biol CORRECTION.png|400px|link=Prasuhn 2021 Front Cell Dev Biol]]
:::: 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«]]
:::: '''22.''' Prasuhn J, Davis RL, Kumar KR (2021) Targeting mitochondrial impairment in Parkinson's disease: challenges and opportunities. '''Front Cell Dev Biol''' 8:615461. - [[Prasuhn 2021 Front Cell Dev Biol |»Bioblast link«]]
<br>
<br>


:::::: [[File:Zhang 2018 Mil Med Res CORRECTION.png|400px|link=Zhang 2018 Mil Med Res]]
:::::: [[File:Gallinat 2022 Int J Mol Sci CORRECTION.png|400px|link=Gallinat 2022 Int J Mol Sci]]
:::: 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«]]
:::: '''23.''' Gallinat A, Vilahur G, Padró T, Badimon L (2022) Network-assisted systems biology analysis of the mitochondrial proteome in a pre-clinical model of ischemia, revascularization and post-conditioning. '''Int J Mol Sci''' 23:2087. - [[Gallinat 2022 Int J Mol Sci |»Bioblast link«]]
<br>
<br>


:::::: [[File:Polyzos 2017 Mech Ageing Dev CORRECTION.png|400px|link=Polyzos 2017 Mech Ageing Dev]]
:::::: [[File:Turton 2021 Expert Opinion Orphan Drugs CORRECTION.png|400px|link=Turton 2021 Expert Opinion Orphan Drugs]]
:::: 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«]]
:::: '''24.''' 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 Orphan Drugs''' 9:151-60. - [[Turton 2021 Expert Opinion Orphan Drugs |»Bioblast link«]]
<br>
<br>


:::::: [[File:Jones, Bennett 2017 Chapter 4 CORRECTION.png|400px|link=Jones 2017 Elsevier]]
:::::: [[File:Keidar 2023 Front Physiol CORRECTION.png|400px|link=Keidar 2023 Front Physiol]]
:::: 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«]]
:::: '''25.''' Keidar N, Peretz NK, Yaniv Y (2023) Ca<sup>2+</sup> pushes and pulls energetics to maintain ATP balance in atrial cells: computational insights. '''Front Physiol''' 14:1231259. - [[Keidar 2023 Front Physiol |»Bioblast link«]]
<br>
<br>


:::::: [[File:DeBerardinis, Chandel 2016 CORRECTION.png|600px|link=DeBerardinis 2016 Sci Adv]]
:::::: [[File:Chakrabarty 2021 Cell Stem Cell 3 CORRECTION.png|400px|link=Chakrabarty 2021 Cell Stem Cell]]
:::: Ref. [25] DeBerardinis RJ, Chandel NS (2016) Fundamentals of cancer metabolism. Sci Adv 2:e1600200. - [[DeBerardinis 2016 Sci Adv |»Bioblast link«]]
:::: '''26.''' Chakrabarty RP, Chandel NS (2021) Mitochondria as signaling organelles control mammalian stem cell fate. '''Cell Stem Cell''' 28:394-408. - [[Chakrabarty 2021 Cell Stem Cell |»Bioblast link«]]
<br>
<br>


:::::: [[File:Nsiah-Sefaa 2016 Bioscie Reports CORRECTION.png|600px|link=Nsiah-Sefaa 2016 Biosci Rep]]
:::::: [[File:Vargas-Mendoza 2021 Life (Basel) CORRECTION.png|400px|link=Vargas-Mendoza 2021 Life (Basel)]]
:::: 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«]]
:::: '''27.''' Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, Madrigal-Santillán EO, Morales-Martínez M, Madrigal-Bujaidar E, Álvarez-González I, Gutiérrez-Salinas J, Esquivel-Chirino C, Chamorro-Cevallos G, Cristóbal-Luna JM, Morales-González JA (2021) Oxidative stress, mitochondrial function and adaptation to exercise: new perspectives in nutrition. '''Life (Basel)''' 11:1269. - [[Vargas-Mendoza 2021 Life (Basel) |»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>
<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:Egan 2023 Physiol Rev CORRECTION.png|400px|link=Egan 2023 Physiol Rev]]
:::: 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«]]
:::: '''28.''' Egan B, Sharples AP (2023) Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training. '''Physiol Rev''' 103:2057-2170. - [[Egan 2023 Physiol Rev |»Bioblast link«]]
<br>
<br>


:::::: [[File:Benard 2011 Springer CORRECTION.png|500px|link=Benard 2011 Springer]]
:::::: [[File:Han 2021 Am J Respir Cell Mol Biol CORRECTION.png|400px|link=Han 2021 Am J Respir Cell Mol Biol]]
:::: 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«]]
:::: '''29.''' Han S, Chandel NS (2021) Lessons from cancer metabolism for pulmonary arterial hypertension and fibrosis. '''Am J Respir Cell Mol Biol''' 65:134-45. - [[Han 2021 Am J Respir Cell Mol Biol |»Bioblast link«]]
<br>
<br>


:::::: [[File:Nussbaum 2005 J Clin Invest CORRECTION.png|500px|link=Nussbaum 2005 J Clin Invest]]
:::::: [[File:Lakovou 2022 Front Aging Neurosci CORRECTION.png|400px|link=Iakovou 2022 Front Aging Neurosci]]
:::: 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«]]
:::: '''30.''' Iakovou E, Kourti M (2022) A comprehensive overview of the complex role of oxidative stress in aging, the contributing environmental stressors and emerging antioxidant therapeutic interventions. '''Front Aging Neurosci''' 14:827900. - [[Iakovou 2022 Front Aging Neurosci |»Bioblast link«]]
<br>
<br>


:::::: [[File:Sanchez et al 2001 CORRECTION.png|600px|link=Sanchez 2001 Br J Pharmacol]]
:::::: [[File:Jayasankar 2022 ACS Omega CORRECTION.png|400px|link=Jayasankar 2022 ACS Omega]]
:::: 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«]]
:::: '''31.''' Jayasankar V, Vrdoljak N, Roma A, Ahmed N, Tcheng M, Minden MD, Spagnuolo PA (2022) Novel mango ginger bioactive (2,4,6-trihydroxy-3,5-diprenyldihydrochalcone) inhibits mitochondrial metabolism in combination with Avocatin B. '''ACS Omega''' 7:1682-93. - [[Jayasankar 2022 ACS Omega |»Bioblast link«]]
<br>
<br>


:::::: [[File:Himms-Hagen, Harper 2001 CORRECTION.png|250px|link=Himms-Hagen 2001 Exp Biol Med (Maywood)]]
:::::: [[File:Yuan 2022 Oxid Med Cell Longev CORRECTION.png|400px|link=Yuan 2022 Oxid Med Cell Longev]]
:::: 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«]]
:::: '''32.''' Yuan Q, Zeng ZL, Yang S, Li A, Zu X, Liu J (2022) Mitochondrial stress in metabolic inflammation: modest benefits and full losses. '''Oxid Med Cell Longev''' 2022:8803404. - [[Yuan 2022 Oxid Med Cell Longev |»Bioblast link«]]
<br>
<br>


:::::: [[File:Brownlee 2001 Nature CORRECTION.png|400px|link=Brownlee 2001 Nature]]
:::::: [[File:Yin 2021 FASEB J CORRECTION.png|400px|link=Yin 2021 FASEB J]]
:::: Ref. [33] Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 14:813-20. - [[Brownlee 2001 Nature |»Bioblast link«]]
:::: '''33.''' 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«]]
:::: 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>
<br>


=== FADH<sub>2</sub>→CII misconceptions: 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.
== Doubles ==


:::::: [[File:OpenStax Biology.png|400px]]
:::::: [[File:Chen 2014 Circ Res CORRECTION.png|400px|link=Chen 2014 Circ Res]]
:::: '''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.
:::: '''1.''' Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. '''Circ Res''' 114:524-37. - [[Chen 2014 Circ Res |»Bioblast link«]]
:::: '''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
<br>
:::: '''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 4''': [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 1
:::: '''Website 5''': [https://www.pharmaguideline.com/2022/01/electron-transport-chain.html Pharmaguideline]


:::::: [[File:Khan Academy modified from OpenStax CORRECTION.png|300px]]
:::::: [[File:Chen 2022 Am J Physiol Cell Physiol CORRECTION.png|400px|link=Chen 2022 Am J Physiol Cell Physiol]]
:::: '''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.''"
:::: '''2.''' Chen CL, Zhang L, Jin Z, Kasumov T, Chen YR (2022) Mitochondrial redox regulation and myocardial ischemia-reperfusion injury. '''Am J Physiol Cell Physiol''' 322:C12-23. - [[Chen 2022 Am J Physiol Cell Physiol |»Bioblast link«]]
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
<br>
<br>


:::::: [[File:Jack Westin CORRECTION.png|400px]]
:::::: [[File:Chen 2022 Int J Mol Sci CORRECTION.png|400px|link=Chen 2022 Int J Mol Sci]]
:::: '''Website 8''': [https://jackwestin.com/resources/mcat-content/oxidative-phosphorylation/electron-transfer-in-mitochondria Jack Westin MCAT Courses]
:::: '''1.''' Chen TH, Koh KY, Lin KM, Chou CK (2022) Mitochondrial dysfunction as an underlying cause of skeletal muscle disorders. '''Int J Mol Sci''' 23:12926. - [[Chen 2022 Int J Mol Sci |»Bioblast link«]]
<br>


:::::: [[File:Expii OpenStax CORRECTION.png|300px]]
:::::: [[File:Schniertshauer 2023 Curr Issues Mol Biol CORRECTION.jpg.png|400px|link=Schniertshauer 2023 Curr Issues Mol Biol]]
:::: '''Website 1''': [https://openstax.org/books/biology/pages/7-4-oxidative-phosphorylation OpenStax Biology] - Fig. 7.12
:::: '''2.''' Schniertshauer D, Wespel S, Bergemann J (2023) Natural mitochondria targeting substances and their effect on cellular antioxidant system as a potential benefit in mitochondrial medicine for prevention and remediation of mitochondrial dysfunctions. '''Curr Issues Mol Biol''' 45:3911-32. - [[Schniertshauer 2023 Curr Issues Mol Biol |»Bioblast link«]]
:::: '''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)
<br>
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By CNX OpenStax
 
:::::: [[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
 
:::::: [[File:Biologydictionary.net CORRECTION.png|400px]]
:::: '''Website 4''': [https://courses.lumenlearning.com/wm-biology1/chapter/reading-electron-transport-chain/ lumen Biology for Majors I] - Fig. 3
:::: '''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 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]
:::: '''Website 13''': [https://www.quora.com/Why-does-FADH2-form-2-ATP Quora]
:::: '''Website 14''': [https://teachmephysiology.com/biochemistry/atp-production/electron-transport-chain/ TeachMePhysiology] -  Fig. 1. 2023-03-13
:::: '''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]]
:::: '''Website 17''': [https://researchtweet.com/mitochondrial-electron-transport-chain-2/ researchtweet]
:::: '''Website 18''': [https://microbenotes.com/electron-transport-chain/ Microbe Notes]
 
:::::: [[File:BiochemDen CORRECTION.png|400px]]
:::: '''Website 19''': [https://biochemden.com/electron-transport-chain-mechanism/ BiochemDen.com]
 
:::::: [[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]
:::: '''Website 21''': [https://vectormine.com/item/electron-transport-chain-as-respiratory-embedded-transporters-outline-diagram/ VectorMine]
 
:::::: [[File:Creative-biolabs CORRECTION.png|400px]]
:::: '''Website 22''': [https://www.creative-biolabs.com/drug-discovery/therapeutics/electron-transport-chain.htm creative-biolabs]
 
:::::: [[File:Khan Academy CORRECTION.png|400px]]
:::: '''Website 6''': [https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc Khan Academy]
:::: '''Website 7''': [https://learn.saylor.org/mod/page/view.php?id=32815 Saylor Academy]
 
:::::: [[File:Expii-Whitney, Rolfes 2002 CORRECTION.png|400px]]
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Whitney, Rolfes 2002
 
:::::: [[File:FlexBooks 2 0 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
 
:::::: [[File:Hyperphysics CORRECTION.png|400px]]
:::: '''Website 24''': [http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/Complex1.html hyperphysics]
 
:::::: [[File:Labster Theory CORRECTION.png|400px]]
:::: '''Website 25''': [https://theory.labster.com/Electron_Transport_Chain/ Labster Theory]
 
:::::: [[File:Nau.edu CORRECTION.png|400px]]
:::: '''Website 26''': [https://www2.nau.edu/~fpm/bio205/u4fg36.html nau.edu]
 
:::::: [[File:Quizlet CORRECTION.png|400px]]
:::: '''Website 27''': [https://quizlet.com/245664214/electron-transport-chain-facts-of-cell-respiration-diagram/ Quizlet]
 
:::::: [[File:ScienceDirect 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]
 
:::::: [[File:ScienceFacts CORRECTION.png|400px]]
:::: '''Website 29''': [https://www.sciencefacts.net/electron-transport-chain.html ScienceFacts]
 
:::::: [[File:SNC1D CORRECTION.png|400px]]
:::: '''Website 30''': [https://sbi4uraft2014.weebly.com/electron-transport-chain.html SNC1D - BIOLOGY LESSON PLAN BLOG]
 
:::::: [[File:Unm.edu CORRECTION.png|400px]]
:::: '''Website 31''': [https://www.unm.edu/~lkravitz/Exercise%20Phys/ETCstory.html unm.edu]
 
:::::: [[File:Wikimedia ETC 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
:::: '''Website 32''': [https://commons.wikimedia.org/wiki/File:Mitochondrial_electron_transport_chain.png Wikimedia]
 
:::::: [[File:YouTube Dirty Medicine Biochemistry 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
 
:::::: [[File:YouTube sciencemusicvideos 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
 
:::::: [[File:ThoughtCo-Getty Images CORRECTION.png|400px]]
:::: '''Website 15''': [https://www.thoughtco.com/electron-transport-chain-and-energy-production-4136143 ThoughtCo] - extender01 / iStock / Getty Images Plus
:::: '''Website 17''': [https://www.dreamstime.com/royalty-free-stock-photography-electron-transport-chain-illustration-oxidative-phosphorylation-image36048617 dreamstime]
 
 
== 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]]
:::: 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]]
:::: 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>.
 
:::::: [[File:Expii-Gabi Slizewska CORRECTION.png|600px]]
:::: '''Website 9''': [https://www.expii.com/t/electron-transport-chain-summary-diagrams-10139 expii] - Image source: By Gabi Slizewska
 
::::* "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]]).
::::::* ''Ref 6'': Tzagoloff A (1982) Mitochondria. Plenum, New York.
::::::* This quote is erroneous, since the textbook by [[Tzagoloff 1982 Plenum Press |Tzagoloff (1982)]] represents fatty acid oxidation in figures and text without any involvement of CII.
 
:::::: [[File:FAO-CII Medical Biochemistry Page.jpg|400px|right|link=https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/]]
:::: '''Website 35''': [https://themedicalbiochemistrypage.org/oxidative-phosphorylation-related-mitochondrial-functions/ The Medical Biochemistry Page (accessed 2023-03-16)]


:::: '''Website 36''': [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'.


:::: '''Website 37''': [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>.
:::: [[Gnaiger_2023_MitoFit_CII#Beyond_version_6 |'''and more ..''']]




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Latest revision as of 08:21, 22 March 2024


high-resolution terminology - matching measurements at high-resolution


Complex II ambiguities

Description

CII-ambiguities Graphical abstract.png

The current narrative that the reduced coenzymes NADH and FADH2 feed electrons from the tricarboxylic acid (TCA) cycle into the mitochondrial electron transfer system can create ambiguities around respiratory Complex CII. Succinate dehydrogenase or CII reduces FAD to FADH2 in the canonical forward TCA cycle. However, some graphical representations of the membrane-bound electron transfer system (ETS) depict CII as the site of oxidation of FADH2. This leads to the false believe that FADH2 generated by electron transferring flavoprotein (CETF) in fatty acid oxidation and mitochondrial glycerophosphate dehydrogenase (CGpDH) feeds electrons into the ETS through CII. In reality, NADH and succinate produced in the TCA cycle are the substrates of Complexes CI and CII, respectively, and the reduced flavin groups FMNH2 and FADH2 are downstream products of CI and CII, respectively, carrying electrons from CI and CII into the Q-junction. Similarly, CETF and CGpDH feed electrons into the Q-junction but not through CII. The ambiguities surrounding Complex II in the literature call for quality control, to secure scientific standards in current communications on bioenergetics and support adequate clinical applications.

Abbreviation: CII ambiguities

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

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

A game of cards

33 copies or variations of a CII ambiguity theme
Martell 2023 Nat Commun CORRECTION.png
1. Martell E, Kuzmychova H, Kaul E, Senthil H, Chowdhury SR, Morrison LC, Fresnoza A, Zagozewski J, Venugopal C, Anderson CM, Singh SK, Banerji V, Werbowetski-Ogilvie TE, Sharif T (2023) Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma. Nat Commun 14:2502. - »Bioblast link«


Solhaug 2023 Cytotechnology CORRECTION.png
2. Solhaug A, Gjessing M, Sandvik M, Eriksen GS (2023) The gill epithelial cell lines RTgill-W1, from Rainbow trout and ASG-10, from Atlantic salmon, exert different toxicity profiles towards rotenone. Cytotechnology 75:63-75. - »Bioblast link«


Fahimi 2022 Trends in Chemistry CORRECTION.png
3. Fahimi P, Matta CF (2022) The hot mitochondrion paradox: reconciling theory and experiment. Trends in Chemistry 4:4-20. - »Bioblast link«


Foo 2022 Trends Microbiol CORRECTION.png
4. Foo J, Bellot G, Pervaiz S, Alonso S (2022) Mitochondria-mediated oxidative stress during viral infection. Trends Microbiol 30:679-92. - »Bioblast link«


Joshi 2022 Biomolecules CORRECTION.png
5. Joshi A, Ito T, Picard D, Neckers L (2022) The mitochondrial HSP90 paralog TRAP1: structural dynamics, interactome, role in metabolic regulation, and inhibitors. Biomolecules 12:880. - »Bioblast link«


Manickam 2022 J Control Release CORRECTION.png
6. Manickam DS (2022) Delivery of mitochondria via extracellular vesicles - a new horizon in drug delivery. J Control Release 343:400-7. - »Bioblast link«


Wu 2022 Neuromolecular Med CORRECTION.png
7. Wu Z, Ho WS, Lu R (2022) Targeting mitochondrial oxidative phosphorylation in glioblastoma therapy. Neuromolecular Med 24:18-22. - »Bioblast link«


Yang 2022 J Cleaner Production CORRECTION.png
8. Yang Y, Zhang X, Hu X, Zhao J, Chen X, Wei X, Yu X (2022) Analysis of the differential metabolic pathway of cultured Chlorococcum humicola with hydroquinone toxic sludge extract. J Cleaner Production 370:133486. - »Bioblast link«


Ignatieva 2021 Int J Mol Sci CORRECTION.png
9. Ignatieva E, Smolina N, Kostareva A, Dmitrieva R (2021) Skeletal muscle mitochondria dysfunction in genetic neuromuscular disorders with cardiac phenotype. Int J Mol Sci 22:7349. - »Bioblast link«


Anoar 2021 Front Neurosci CORRECTION.jpg
10. Anoar S, Woodling NS, Niccoli T (2021) Mitochondria dysfunction in frontotemporal dementia/amyotrophic lateral sclerosis: lessons from Drosophila models. Front Neurosci 15:786076. - »Bioblast link«


Shields 2021 Front Cell Dev Biol CORRECTION.png
11. Shields HJ, Traa A, Van Raamsdonk JM (2021) Beneficial and detrimental effects of reactive oxygen species on lifespan: a comprehensive review of comparative and experimental studies. Front Cell Dev Biol 9:628157. - »Bioblast link«


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


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


Aye 2022 Am J Obstet Gynecol CORRECTION.png
14. Aye ILMH, Aiken CE, Charnock-Jones DS, Smith GCS (2022) Placental energy metabolism in health and disease-significance of development and implications for preeclampsia. Am J Obstet Gynecol 226:S928-44. - »Bioblast link«


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


Cojocaru 2023 Antioxidants (Basel) CORRECTION.png
16. Cojocaru KA, Luchian I, Goriuc A, Antoci LM, Ciobanu CG, Popescu R, Vlad CE, Blaj M, Foia LG (2023) Mitochondrial dysfunction, oxidative stress, and therapeutic strategies in diabetes, obesity, and cardiovascular disease. Antioxidants (Basel) 12:658. - »Bioblast link«


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


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


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


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


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


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


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


Turton 2021 Expert Opinion Orphan Drugs CORRECTION.png
24. 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 Orphan Drugs 9:151-60. - »Bioblast link«


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


Chakrabarty 2021 Cell Stem Cell 3 CORRECTION.png
26. Chakrabarty RP, Chandel NS (2021) Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell 28:394-408. - »Bioblast link«


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


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


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


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


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


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


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



Doubles

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


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



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


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



and more ..


MitoPedia concepts: MiP concept 





MitoPedia topics: Enzyme, Substrate and metabolite 


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MitoPedia:FAT4BRAIN 

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