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Gnaiger 2024 J Biol Chem

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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

» PMID: 38118236 Open Access

Gnaiger Erich (2024) J Biol Chem

Abstract:

CII-ambiguities Graphical abstract.png

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). CII is the only membrane-bound enzyme in the tricarboxylic acid cycle and is part of the electron transfer system of the mitochondrial inner membrane feeding electrons into the coenzyme Q-junction. 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 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

ORCID: ORCID.png Gnaiger Erich, Oroboros Instruments, Innsbruck, Austria

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

MitoFit Preprint

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
Living Communication with updated references on CII ambiguities.

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SDH: FAD ⟶ FADH2; CII: FADH2 ⟶ FAD

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FADH2 ⟶ FAD

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FADH2 ⟶ FAD+ (+H+ or +2H+)

FADH2 ⟶ FAD+
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While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH2 as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate.


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FADH2 ⟶ FAD+ + H+
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FADH2 ⟶ FAD+ + 2H+
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FADH2 ⟶ FAD2+
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FADH2 ⟶ FADH or FADH+

FADH2 ⟶ FADH
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6a.6. Ref 327 Steiner JL, Lang CH (2017) Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis. Int J Biochem Cell Biol 89:125-35. - »Bioblast link«


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6a.7. Ref 328 Tabassum N, Kheya IS, Ibn Asaduzzaman SA, Maniha SM, Fayz AH, Zakaria A, Fayz AH, Zakaria A, Noor R (2020) A review on the possible leakage of electrons through the electron transport chain within mitochondria. J Biomed Res Environ Sci 1:105-13. - »Bioblast link«


Yang 2020 Transl Neurodegener CORRECTION.png
6a.8. Ref 329 Yang L, Youngblood H, Wu C, Zhang Q (2020) Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation. Transl Neurodegener 9:19. - »Bioblast link«


Yu 2023 Antioxidants (Basel) CORRECTION.png
6a.9. Ref 330 Yu T, Wang L, Zhang L, Deuster PA (2023) Mitochondrial fission as a therapeutic target for metabolic diseases: insights into antioxidant strategies. Antioxidants (Basel) 12:1163. - »Bioblast link«


FADH2 ⟶ FADH +H+
Burgin 2020 FEBS Lett CORRECTION.png
6b.1. Ref 331 Burgin HJ, McKenzie M (2020) Understanding the role of OXPHOS dysfunction in the pathogenesis of ECHS1 deficiency. FEBS Lett 594:590-610. - »Bioblast link«


FADH2 ⟶ FADH+
Achreja 2022 Nat Metab CORRECTION.png
6c.1. Ref 332 Achreja A, Yu T, Mittal A, Choppara S, Animasahun O, Nenwani M, Wuchu F, Meurs N, Mohan A, Jeon JH, Sarangi I, Jayaraman A, Owen S, Kulkarni R, Cusato M, Weinberg F, Kweon HK, Subramanian C, Wicha MS, Merajver SD, Nagrath S, Cho KR, DiFeo A, Lu X, Nagrath D (2022) Metabolic collateral lethal target identification reveals MTHFD2 paralogue dependency in ovarian cancer. Nat Metab 4:1119-37. - »Bioblast link«


Torres 2017 Cell Metab CORRECTION.png
6c.2. Ref 333 Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, Neufer PD (2018) 17β-estradiol directly lowers mitochondrial membrane microviscosity and improves bioenergetic function in skeletal muscle. Cell Metab 27:167-79. - »Bioblast link«


FADH or FADH+ ⟶

Johnson 2013 Eukaryot Cell CORRECTION.png
7a.1. Ref 334 Johnson X, Alric J (2013) Central carbon metabolism and electron transport in Chlamydomonas reinhardtii: metabolic constraints for carbon partitioning between oil and starch. Eukaryot Cell 12:776-93. - »Bioblast link«


Kuznetsov 2022 Antioxidants (Basel) CORRECTION.png
7a.2. Ref 335 Kuznetsov AV, Margreiter R, Ausserlechner MJ, Hagenbuchner J (2022) The complex interplay between mitochondria, ROS and entire cellular metabolism. Antioxidants (Basel) 11:1995. - »Bioblast link«


FADH ⟶ FAD
Diaz 2023 Front Mol Biosci CORRECTION.png
7b.1. Ref 336 Diaz EC, Adams SH, Weber JL, Cotter M, Børsheim E (2023) Elevated LDL-C, high blood pressure, and low peak V˙O2 associate with platelet mitochondria function in children-The Arkansas Active Kids Study. Front Mol Biosci 10:1136975. - »Bioblast link«


Jezek 2023 Antioxid Redox Signal CORRECTION.png
7b.2. Ref 337 Ježek P, Jabůrek M, Holendová B, Engstová H, Dlasková A (2023) Mitochondrial cristae morphology reflecting metabolism, superoxide formation, redox homeostasis, and pathology. Antioxid Redox Signal. - »Bioblast link«


FADH ⟶ FAD+
Grasso 2020 Cell Stress CORRECTION.png
7c.1. Ref 338 Grasso D, Zampieri LX, Capelôa T, Van de Velde JA, Sonveaux P (2020) Mitochondria in cancer. Cell Stress 4:114-46. - »Bioblast link«


Middleton 2021 Therap Adv CORRECTION.png
7c.2. Ref 339 Middleton P, Vergis N (2021) Mitochondrial dysfunction and liver disease: role, relevance, and potential for therapeutic modulation. Therap Adv Gastroenterol 14:17562848211031394. - »Bioblast link«


Moudgil 2005 J Appl Physiol (1985) CORRECTION.png
7c.3. Ref 340 Moudgil R, Michelakis ED, Archer SL (2005) Hypoxic pulmonary vasoconstriction. J Appl Physiol (1985) 98:390-403. - »Bioblast link«


FADH ⟶ FAD+ +H+
Puntel 2013 Toxicol In Vitro CORRECTION.png
7d.1. Ref 341 Puntel RL, Roos DH, Seeger RL, Rocha JB (2013) Mitochondrial electron transfer chain complexes inhibition by different organochalcogens. Toxicol In Vitro 27:59-70. - »Bioblast link«


FADH ⟶ FAD +2H+
Xing 2022 Atlantis Press CORRECTION.png
7e.1. Ref 342 Xing Yunxie (2022) Is genome instability a significant cause of aging? A review. Atlantis Press. - »Bioblast link«


FADH+ ⟶ FAD
Catania 2019 Orphanet J Rare Dis CORRECTION.png
7f.1. Ref 343 Catania A, Iuso A, Bouchereau J, Kremer LS, Paviolo M, Terrile C, Bénit P, Rasmusson AG, Schwarzmayr T, Tiranti V, Rustin P, Rak M, Prokisch H, Schiff M (2019) Arabidopsis thaliana alternative dehydrogenases: a potential therapy for mitochondrial complex I deficiency? Perspectives and pitfalls. Orphanet J Rare Dis 14:236. - »Bioblast link«


FAD or FAD+ ⟶ or other

FAD ⟶
Ahmad 2017 Springer, Cham CORRECTION.png
8a.1. Ref 344 Ahmad G, Almasry M, Dhillon AS, Abuayyash MM, Kothandaraman N, Cakar Z (2017) Overview and sources of reactive oxygen species (ROS) in the reproductive system. In: Agarwal A, et al (eds) Oxidative stress in human reproduction. Springer, Cham. - »Bioblast link«


Irazabal 2020 Cells CORRECTION.png
8a.2. Ref 345 Irazabal MV, Torres VE (2020) Reactive oxygen species and redox signaling in chronic kidney disease. Cells 9:1342. - »Bioblast link«


LaMoia 2022 Proc Natl Acad Sci U S A CORRECTION.png
8a.3. Ref 346 LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI (2022) Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proc Natl Acad Sci U S A 119:e2122287119. - »Bioblast link«


FAD+ ⟶ FADH2
Chinopoulos 2013 J Neurosci Res CORRECTION.png
8b.1. Ref 347 Chinopoulos C (2013) Which way does the citric acid cycle turn during hypoxia? The critical role of α-ketoglutarate dehydrogenase complex. J Neurosci Res 91:1030-43. - »Bioblast link«


FADH2+ Succinate ⟶ Fumarate +2H+
Andrieux 2021 Int J Mol Sci CORRECTION.png
8c.1. Ref 348 Andrieux P, Chevillard C, Cunha-Neto E, Nunes JPS (2021) Mitochondria as a cellular hub in infection and inflammation. Int J Mol Sci 22:11338. - »Bioblast link«


FADH2 ⟶ CI ⟶ CII
Huss 2005 J Clin Invest CORRECTION.png
8d.1. Ref 349 Huss JM, Kelly DP (2005) Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest 115:547-55. - »Bioblast link«


ETF ⟶ CII
Picard 2018 Biol Psychiatry CORRECTION.png
8e.1. Ref 350 Bindra S, McGill MA, Triplett MK, Tyagi A, Thaker PH, Dahmoush L, Goodheart MJ, Ogden RT, Owusu-Ansah E, R Karan K, Cole S, Sood AK, Lutgendorf SK, Picard M (2021) Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors. Sci Rep 11:11595. - »Bioblast link«
Bugarski 2018 Am J Physiol Renal Physiol CORRECTION.png
8e.2. Ref 351 Bugarski M, Martins JR, Haenni D, Hall AM (2018) Multiphoton imaging reveals axial differences in metabolic autofluorescence signals along the kidney proximal tubule. Am J Physiol Renal Physiol 315:F1613-25. - »Bioblast link«


Cortassa 2019 Front Physiol CORRECTION.png
8e.3. Ref 352 Cortassa S, Aon MA, Sollott SJ (2019) Control and regulation of substrate selection in cytoplasmic and mitochondrial catabolic networks. A systems biology analysis. Front Physiol 10:201. - »Bioblast link«


Picard 2018 Biol Psychiatry CORRECTION.png
8e.4. Ref 353 Karan KR, Trumpff C, McGill MA, Thomas JE, Sturm G, Lauriola V, Sloan RP, Rohleder N, Kaufman BA, Marsland AL, Picard M (2020) Mitochondrial respiratory capacity modulates LPS-induced inflammatory signatures in human blood. Brain Behav Immun Health 5:100080. - »Bioblast link«
8e.5. Ref 354 Picard M, McEwen BS (2018) Psychological stress and mitochondria: a systematic review. Psychosom Med 80:141-53. - »Bioblast link«
8e.6. Ref 355 Picard M, Prather AA, Puterman E, Cuillerier A, Coccia M, Aschbacher K, Burelle Y, Epel ES (2018) A mitochondrial health index sensitive to mood and caregiving stress. Biol Psychiatry 84:9-17. - »Bioblast link«
8e.7. Ref 356 Rausser S, Trumpff C, McGill MA, Junker A, Wang W, Ho SH, Mitchell A, Karan KR, Monk C, Segerstrom SC, Reed RG, Picard M (2021) Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures. Elife 10:e70899. - »Bioblast link«



FAO and CII ambiguitiy

Balasubramaniam 2020 J Transl Genet Genom CORRECTION.png
Ref 50 Balasubramaniam S, Yaplito-Lee J (2020) Riboflavin metabolism: role in mitochondrial function. J Transl Genet Genom 4:285-306. - »Bioblast link«


Bertero 2018 Nat Rev Cardiol CORRECTION.png
Ref 192 Bertero E, Maack C (2018) Metabolic remodelling in heart failure. Nat Rev Cardiol 15:457-70. - »Bioblast link«


Bugarski 2018 Am J Physiol Renal Physiol CORRECTION.png
Ref 351 Bugarski M, Martins JR, Haenni D, Hall AM (2018) Multiphoton imaging reveals axial differences in metabolic autofluorescence signals along the kidney proximal tubule. Am J Physiol Renal Physiol 315:F1613-25. - »Bioblast link«


Cortassa 2019 Front Physiol CORRECTION.png
Ref 352 Cortassa S, Aon MA, Sollott SJ (2019) Control and regulation of substrate selection in cytoplasmic and mitochondrial catabolic networks. A systems biology analysis. Front Physiol 10:201. - »Bioblast link«


DiMauro 2003 N Engl J Med CORRECTION.png
Ref 202 DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348:2656-68. - »Bioblast link«


Esparza-Molto 2020 Antioxid Redox Signal CORRECTION.png
Ref 62 Esparza-Moltó PB, Cuezva JM (2020) Reprogramming oxidative phosphorylation in cancer: a role for RNA-binding proteins. Antioxid Redox Signal 33:927-45. - »Bioblast link«


Frangos 2023 J Biol Chem CORRECTION.png
Ref 205 Frangos SM, DesOrmeaux GJ, Holloway GP (2023) Acidosis attenuates CPT-I supported bioenergetics as a potential mechanism limiting lipid oxidation. J Biol Chem 299:105079. - »Bioblast link«


Hinder 2019 Sci Rep CORRECTION.png
Ref 71 Hinder LM, Sas KM, O'Brien PD, Backus C, Kayampilly P, Hayes JM, Lin CM, Zhang H, Shanmugam S, Rumora AE, Abcouwer SF, Brosius FC 3rd, Pennathur S, Feldman EL (2019) Mitochondrial uncoupling has no effect on microvascular complications in type 2 diabetes. Sci Rep 9:881. - »Bioblast link«


Huss 2005 J Clin Invest CORRECTION.png
Ref 349 Huss JM, Kelly DP (2005) Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest 115:547-55. - »Bioblast link«


Kikusato 2016 Proc Jpn Soc Anim Nutr Metab CORRECTION.png
Ref 292 Kikusato M, Furukawa K, Kamizono T, Hakamata Y, Toyomizu M (2016) Roles of mitochondrial oxidative phosphorylation and reactive oxygen species generation in the metabolic modification of avian skeletal muscle. Proc Jpn Soc Anim Nutr Metab 60:57-68. - »Bioblast link«


Kraegen 2008 Proc Natl Acad Sci U S A CORRECTION.png
Ref 294 Kraegen EW, Cooney GJ, Turner N (2008) Muscle insulin resistance: a case of fat overconsumption, not mitochondrial dysfunction. Proc Natl Acad Sci U S A 105:7627-8. - »Bioblast link«


Loussouarn 2021 Front Immunol CORRECTION.png
Ref 296 Loussouarn C, Pers YM, Bony C, Jorgensen C, Noël D (2021) Mesenchymal stromal cell-derived extracellular vesicles regulate the mitochondrial metabolism via transfer of miRNAs. Front Immunol 12:623973. - »Bioblast link«


Ma 2018 Cancer Lett CORRECTION.png
Ref 291 Ma Y, Temkin SM, Hawkridge AM, Guo C, Wang W, Wang XY, Fang X (2018) Fatty acid oxidation: an emerging facet of metabolic transformation in cancer. Cancer Lett 435:92-100. - »Bioblast link«


Ma 2020 Sci Rep CORRECTION.png
Ref 292 Ma Y, Wang W, Devarakonda T, Zhou H, Wang XY, Salloum FN, Spiegel S, Fang X (2020) Functional analysis of molecular and pharmacological modulators of mitochondrial fatty acid oxidation. Sci Rep 10:1450. - »Bioblast link«


Massart 2013 Curr Pathobiol Rep CORRECTION.png
Ref 81 Massart J, Begriche K, Buron N, Porceddu M, Borgne-Sanchez A, Fromenty B (2013) Drug-induced inhibition of mitochondrial fatty acid oxidation and steatosis. Curr Pathobiol Rep 1:147–57. - »Bioblast link«


Merritt 2020 Rev Endocr Metab Disord CORRECTION.png
Ref 291 Merritt JL 2nd, MacLeod E, Jurecka A, Hainline B (2020) Clinical manifestations and management of fatty acid oxidation disorders. Rev Endocr Metab Disord 21:479-93. - »Bioblast link«


Murray 2009 Genome Med CORRECTION.png
Ref 221 Murray AJ (2009) Metabolic adaptation of skeletal muscle to high altitude hypoxia: how new technologies could resolve the controversies. Genome Med 1:117. - »Bioblast link«


Picard 2012 Am J Respir Crit Care Med CORRECTION.png
Ref 226 Picard M, Jung B, Liang F, Azuelos I, Hussain S, Goldberg P, Godin R, Danialou G, Chaturvedi R, Rygiel K, Matecki S, Jaber S, Des Rosiers C, Karpati G, Ferri L, Burelle Y, Turnbull DM, Taivassalo T, Petrof BJ (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186:1140-9. - »Bioblast link«


Picard 2018 Biol Psychiatry CORRECTION.png
Ref 354 Picard M, McEwen BS (2018) Psychological stress and mitochondria: a systematic review. Psychosom Med 80:141-53. - »Bioblast link«
Ref 355 Copied by: Picard M, Prather AA, Puterman E, Cuillerier A, Coccia M, Aschbacher K, Burelle Y, Epel ES (2018) A mitochondrial health index sensitive to mood and caregiving stress. Biol Psychiatry 84:9-17. - »Bioblast link«
Ref 353 Copied by: Karan KR, Trumpff C, McGill MA, Thomas JE, Sturm G, Lauriola V, Sloan RP, Rohleder N, Kaufman BA, Marsland AL, Picard M (2020) Mitochondrial respiratory capacity modulates LPS-induced inflammatory signatures in human blood. Brain Behav Immun Health 5:100080. - »Bioblast link«
Ref 350 Copied by: Bindra S, McGill MA, Triplett MK, Tyagi A, Thaker PH, Dahmoush L, Goodheart MJ, Ogden RT, Owusu-Ansah E, R Karan K, Cole S, Sood AK, Lutgendorf SK, Picard M (2021) Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors. Sci Rep 11:11595. - »Bioblast link«
Ref 356 Copied by: Rausser S, Trumpff C, McGill MA, Junker A, Wang W, Ho SH, Mitchell A, Karan KR, Monk C, Segerstrom SC, Reed RG, Picard M (2021) Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures. Elife 10:e70899. - »Bioblast link«


Prasun 2020 J Diabetes Metab Disord CORRECTION.png
Ref 228 Prasun P (2020) Role of mitochondria in pathogenesis of type 2 diabetes mellitus. J Diabetes Metab Disord 19:2017-22. - »Bioblast link«


Rinaldo 2002 Annu Rev Physiol CORRECTION.png
Ref 300 Rinaldo P, Matern D, Bennett MJ (2002) Fatty acid oxidation disorders. Annu Rev Physiol 64:477-502. - »Bioblast link«
Ref 284 Bennett MJ, Sheng F, Saada A (2020) Biochemical assays of TCA cycle and β-oxidation metabolites. Methods Cell Biol 155:83-120. - »Bioblast link«


Toleikis 2020 Cells CORRECTION.png
Ref 97 Toleikis A, Trumbeckaite S, Liobikas J, Pauziene N, Kursvietiene L, Kopustinskiene DM (2020) Fatty acid oxidation and mitochondrial morphology changes as key modulators of the affinity for ADP in rat heart mitochondria. Cells 9:340. - »Bioblast link«


Vockley 2021 Cambridge Univ Press CORRECTION.png
Ref 237 Vockley J (2021) Inborn errors of fatty acid oxidation. In: Suchy FS, Sokol RJ, Balistreri WF (eds) Liver disease in children. Cambridge Univ Press:611-27. https://doi.org/10.1017/9781108918978.034 - »Bioblast link«


Zhang 2021 Cells CORRECTION.png
Ref 240 Zhang X, Tomar N, Kandel SM, Audi SH, Cowley AW Jr, Dash RK (2021) Substrate- and calcium-dependent differential regulation of mitochondrial oxidative phosphorylation and energy production in the heart and kidney. Cells 11:131. - »Bioblast link«



From CGpDH and other pathways to FADH2 to CII

Blanco 2017 Academic Press CORRECTION.png /// Willson 2022 Blood CORRECTION.png /// Rai 2022 G3 (Bethesda) CORRECTION.png /// Koopman 2016 Nat Protoc CORRECTION.png

Comment (Cardoso Luiza, Gnaiger Erich, 2023-08-06):

Fig. 9.19 from Blanco, Blanco (2017), Fig. 1 from Willson et al (2022), and Fig. 1 from Rai et al (2022) show FADH2 (1) to be formed in the mitochondrial matrix from GPDH, GPD2, or GPO1 (all indicating CGpDH) and from the TCA cycle (Fig. 1 Rai et al (2022)), then (2) feeding electrons further 'To respiratory chain', the 'ETC', or 'Electron Transport Chain' (ETS). Combined with FADH2 shown (1) to be formed in the mt-matrix from the TCA cycle and (2) feeding into CII (Fig. 1 from Koopman et al (2016); among >120 examples discussed as CII-ambiguities), one may arrive at the erroneous conclusion on a direct role of CII in the oxidation of glycerophosphate, analogous to false representations of CII involved in fatty acid oxidation.

Blanco 2017 Academic Press CORRECTION.png
Ref 366 Blanco A, Blanco G (2017) Chapter 9 - Biological oxidations: bioenergetics. In Blanco A, Blanco G, eds, Medical biochemistry. Academic Press:177-204. - »Bioblast link«


Cogliati 2021 Biochem Soc Trans CORRECTION.png
Ref 59 Cogliati S, Cabrera-Alarcón JL, Enriquez JA (2021) Regulation and functional role of the electron transport chain supercomplexes. Biochem Soc Trans 49:2655-68. - »Bioblast link«


Covarrubias 2021 Nat Rev Mol Cell Biol CORRECTION.png
Ref 367 Covarrubias AJ, Perrone R, Grozio A, Verdin E (2021) NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 22:119-41. - »Bioblast link«


Hashimoto 2006 Am J Physiol Endocrinol Metab CORRECTION.png
Ref 368 Hashimoto T, Hussien R, Brooks GA (2006) Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex. Am J Physiol Endocrinol Metab 290:E1237-44. - »Bioblast link«


LaMoia 2022 Proc Natl Acad Sci U S A CORRECTION.png
Ref 346 LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI (2022) Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proc Natl Acad Sci U S A 119:e2122287119. - »Bioblast link«


Lautrup 2019 Cell Metab CORRECTION.png
Ref 369 Lautrup S, Sinclair DA, Mattson MP, Fang EF (2019) NAD+ in brain aging and neurodegenerative disorders. Cell Metab 30:630-55. - »Bioblast link«


Mosegaard 2020 Int J Mol Sci CORRECTION.png
Ref 84 Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, Olsen RKJ (2020) Riboflavin deficiency-implications for general human health and inborn errors of metabolism. Int J Mol Sci 21:3847. - »Bioblast link«


Willson 2022 Blood CORRECTION.png
Ref 370 Willson JA, Arienti S, Sadiku P, Reyes L, Coelho P, Morrison T, Rinaldi G, Dockrell DH, Whyte MKB, Walmsley SR (2022) Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle. Blood 139:281-6. - »Bioblast link«


Xiao 2018 Antioxid Redox Signal CORRECTION.png
Ref 371 Xiao W, Wang RS, Handy DE, Loscalzo J (2018) NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxid Redox Signal 28:251–72. - »Bioblast link«



CII as a H+ pump

Cronshaw 2019 Photobiomodul Photomed Laser Surg CORRECTION.png
Ref 372 Cronshaw M, Parker S, Arany P (2019) Feeling the heat: evolutionary and microbial basis for the analgesic mechanisms of photobiomodulation therapy. Photobiomodul Photomed Laser Surg 37:517-26. - »Bioblast link«


Dumollard 2007 Development CORRECTION.png
Ref 373 Dumollard R, Ward Z, Carroll J, Duchen MR (2007) Regulation of redox metabolism in the mouse oocyte and embryo. Development 134:455-65. - »Bioblast link«


Jian 2020 Cell Metab CORRECTION.png
Ref 374 Jian C, Fu J, Cheng X, Shen LJ, Ji YX, Wang X, Pan S, Tian H, Tian S, Liao R, Song K, Wang HP, Zhang X, Wang Y, Huang Z, She ZG, Zhang XJ, Zhu L, Li H (2020) Low-dose sorafenib acts as a mitochondrial uncoupler and ameliorates nonalcoholic steatohepatitis. Cell Metab 31:892-908. - »Bioblast link«
While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH2 as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate.


Shirakawa 2023 Sci Rep CORRECTION.png
Ref 304 Shirakawa R, Nakajima T, Yoshimura A, Kawahara Y, Orito C, Yamane M, Handa H, Takada S, Furihata T, Fukushima A, Ishimori N, Nakagawa M, Yokota I, Sabe H, Hashino S, Kinugawa S, Yokota T (2023) Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults. Sci Rep 13:5203. - »Bioblast link«
While CI functions as a proton pump, CII does not. Depicting CII as a proton pump would be analogous to falsely portraying FADH2 as the substrate of CII, as if it were a copy of CI, which functions as a proton pump with NADH as its substrate.


Xing 2022 Atlantis Press CORRECTION.png
Ref 342 Xing Yunxie (2022) Is genome instability a significant cause of aging? A review. Atlantis Press. - »Bioblast link«



Questions.jpg


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Bioblast links: Substrates and cofactors - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
Substrate
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Cofactor
» Cofactor
» Coenzyme, cosubstrate
» Nicotinamide adenine dinucleotide
» Coenzyme Q2
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» 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


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Enzyme: Complex II;succinate dehydrogenase 



Ambiguity crisis, FAT4BRAIN, Publication:FAT4BRAIN