Category:Ambiguity crisis - NAD and H+

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Hydrogen ion ambiguities in the electron transfer system

Communicated by Gnaiger E (2023-10-08) last update 2023-11-10
Electron (e-) transfer linked to hydrogen ion (hydron; H+) transfer is a fundamental concept in the field of bioenergetics, critical for understanding redox-coupled energy transformations.
Ambiguity alert H+.png
However, the current literature contains inconsistencies regarding H+ formation on the negative side of bioenergetic membranes, such as the matrix side of the mitochondrial inner membrane, when NADH is oxidized during oxidative phosphorylation (OXPHOS). Ambiguities arise when examining the oxidation of NADH by respiratory Complex I or succinate by Complex II.
Ambiguity alert e-.png
Oxidation of NADH or succinate involves a two-electron transfer of 2{H++e-} to FMN or FAD, respectively. Figures indicating a single electron e- transferred from NADH or succinate lack accuracy.
Ambiguity alert NAD.png
The oxidized NAD+ is distinguished from NAD indicating nicotinamide adenine dinucleotide independent of oxidation state.
NADH + H+ → NAD+ +2{H++e-} is the oxidation half-reaction in this H+-linked electron transfer represented as 2{H++e-} (Gnaiger 2023). Putative H+ formation shown as NADH → NAD+ + H+ conflicts with chemiosmotic coupling stoichiometries between H+ translocation across the coupling membrane and electron transfer to oxygen. Ensuring clarity in this complex field is imperative to tackle the apparent ambiguity crisis and prevent confusion, particularly in light of the increasing number of interdisciplinary publications on bioenergetics concerning diagnostic and clinical applications of OXPHOS analysis.

Supplement 1. The CI substrate is NADH + H+

In mitochondrial preparations, NADH-generating substrates, N, of various dehydrogenases (pyruvate, glutamate, malate, or other ET-pathway competent N-type substrate combinations) are applied to support respiration through Complex I (Gnaiger 2020). Importantly, malate and other N-type substrates are not CI-substrates.
Bottje 2019 Poult Sci CORRECTION.png
xx Bottje WG (2019) Oxidative metabolism and efficiency: the delicate balancing act of mitochondria. Poult Sci 98:4223-30. - »Bioblast link«
Fig. 1 of Bottje (2019): NADH+H+ should be indicated as substrate of CI compared to succinate as substrate of CII. Their oxidation is a 2-electron reaction.

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Supplement 2. Electron transfer from CI ⟶ CII ⟶ CIII

Q-junction
The term electron transfer system takes into account the convergent structure of mitochondrial pathways merging from various branched routes at the N-junction and Q-junction (Gnaiger 2020). Unfortunately the term electron transport chain is still used in some branches of the bioenergetic literature. Combined with respiratory Complexes defined in numerical sequence as CI, CII, CIII, and CIV, this led to misrepresenting electron transfer as (NADH, FADH2) → CI → CII → CIII:
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xx Cowan K, Anichtchik O, Luo S (2019) Mitochondrial integrity in neurodegeneration. CNS Neurosci Ther 25:825-36. - »Bioblast link«

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

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xx Xia H, Huang Z, Wang Z, Liu S, Zhao X, You J, Xu Y, Yam JWP, Cui Y (2022) Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma. Front Oncol 12:953668. - »Bioblast link«

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Supplement 3. NADH + H+ ⟶ NAD+ + (2)H+ (+2e-)

It is important to distinguish in the oxidation of NADH the H+ that is consumed as a substrate (on the left side of the equation) from the 2H+ that are donated in the redox reaction of H+-linked electron transfer to the reductant FMN:
NADH + H+ ⟶ NAD+ + 2{H++e-}
In H+-linked electron transfer, the 2e- should be matched with 2H+.


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xx Hargreaves IP, Al Shahrani M, Wainwright L, Heales SJR (2016) Drug-induced mitochondrial toxicity. Drug Saf 39:661–74. - »Bioblast link«

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Mathur 2017 Front Cell Neurosci CORRECTION.png
xx Mathur D, Riffo-Campos AL, Castillo J, Haines JD, Vidaurre OG, Zhang F, Coret-Ferrer F, Casaccia P, Casanova B, Lopez-Rodas G (2017) Bioenergetic failure in rat oligodendrocyte progenitor cells treated with cerebrospinal fluid derived from multiple sclerosis poatients. Front Cell Neurosci 11:209. - »Bioblast link«
Fig. 5 of Mathur et al (2017): H+ is consumed in the redox chemical (scalar) reaction of H+-linked electron transfer catalyzed by CI, NADH + H+ → NAD+ + 2H+. This same H+ is shown to be transported in the vectorial H+ translocation from the matrix side across the mtIM (H+neg → H+pos). The scalar and vectorial transformations must be distinguished. When the path is shown of the single electron (instead of 2{H++e-}) from NADH to ubiquinone, then it is particularly confusing when the 2H+ in the H+-linked electron transfer are indicated as remaining in the matrix.

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xx Rosca MG, Vazquez EJ, Chen Q, Kerner J, Kern TS, Hoppel CL (2012) Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen species production in kidney cortical tubules in early diabetes. Diabetes 61:2074-83. - »Bioblast link«
Fig. 5 of Rosca et al (2012): Oxidation of succinate to fumarate reduces ubiquinone to ubiquinol through oxidation of FAD to FADH2 and further redox steps in CII. Likewise, oxidation of NADH + H+ to NAD+ reduces ubiquinone to ubiquinol through oxidation of FMN to FMNH2 and further redox steps in CI. This reduction of UQ to UQH2 effectively consumes the 2H+ together with 2e-. Hence, the 2H+ should not be shown to be formed in the matrix. Indication of H+-linked electron transfer as 2{H++e-} eliminates the ambiguity.

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## Copied with permission from: Hall J (2016) Guyton and Hall Textbook of Medical Physiology. 13. Elsevier, Philadelphia.

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Supplement 4. NADH (+H+) ⟶ NAD+ + e-

4.1. NADH + H+ ⟶ NAD+ + e-

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4.2. NADH ⟶ NAD+ + e-

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xx Vekshin N (2020) Biophysics of mitochondria. Springer Cham: 197 pp. - »Bioblast link«

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4.3. NADH ⟶ e-

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xx Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol 6:524-551. - »Bioblast link«

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Supplement 5. NADH ⟶ NAD+ + H+ (+ 2e-)

In the chemical equation for oxidation of NADH + H+ by CI,
NADH + H+ → NAD+ + 2{H++e-}
H+ linked to electron transfer is indicated as 2{H++e-} on the product side, in contrast to H+ defined as a substrate in the chemical reaction (Gnaiger 2023). This formal distinction avoids an ambiguity arising from writing this equation as (see above),
NADH + H+ → NAD+ + 2H+
Then H+ on both sides of the equation may be considered to cancel, which provides a possible explanation for the frequent occurrence of the erroneous rearrangement as
NADH → NAD+ + H+


5.1. NADH ⟶ NAD+ + H+ + 2e-

Electron flow from NADH to FMN in CI proceeds as a 2e- transfer. The 2e- are never free floating in the matrix but belong to the arrow reaching ubiquinone UQ. 2-electron transfer is linked to 2H+ transfer, hence the meaning of the single H+ — written on the right side of the equation — is elusive.
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xx Tseng W-W, Wei A-C (2022) Kinetic mathematical modeling of oxidative phosphorylation in cardiomyocyte mitochondria. Cells 11:4020. - »Bioblast link«

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Vekshin 2020 Springer Cham 3.2 CORRECTION.png
xx Vekshin N (2020) Biophysics of mitochondria. Springer Cham: 197 pp. - »Bioblast link«

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5.2. NADH ⟶ NAD+ + H+ + e-

The 2-electron transfer from NADH to CI is not well depicted in graphical representations suggesting the equation NADH ⟶ NAD+ + H+ + e-.
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Fig. 1 by Głombik et al (2021): Red arrows indicate e- transfer from NADH through CI to Q and from FADH2 through CII to Q. In oxidation of NADH, one blue H+ appears in the matrix, which is pumped across the mtIM through CI. In fact, reducing equivalents are not pumped but are consumed in the reduction of FMN and further of UQ to UQH2. 2H+ appear in the matrix in oxidation of FADH2. Their fate is not clear (CII is not a H+ pump).

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5.3. NADH ⟶ NAD+ + H+

In many cases the oxidation NADH ⟶ NAD+ + H+ by CI is compared with oxidation by CII of succinate to fumarate, succinate to fumarate + 2H+, FADH2 to FAD, or FADH2 to FAD + 2H+. These combinations underscore the ambiguous nature in these portrayals of the transfer of reducing equivalents. What is the meaning of H+ in the equation NADH ⟶ NAD+ + H+ suggested by the following graphical representations of NADH oxidation by CI?
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xx Bajeli S, Baid N, Kaur M, Pawar GP, Chaudhari VD, Kumar A (2020) Terminal respiratory oxidases: a targetables vulnerability of mycobacterial bioenergetics? Front Cell Infect Microbiol 10:589318. - »Bioblast link«
Fig. 1 by Bejali et al (2020): The meaning of e- attached to various enzymes is not clear. For indication of electron transfer, corresponding arrows should be added.

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Bennekou 2020 OECD CORRECTION.png
xx Bennekou SH, van der Stel W, Carta G, Eakins J, Delp J, Forsby A, Kamp H, Gardner I, Zdradil B, Pastor M, Gomes JC, White A, Steger-Hartman T, Danen EHJ, Leist M, Walker P, Jennings P, van de Water B (2020) Case stuy on the use of integrated approaches to testing and assessment for mitochondrial Complex-III-mediated neurotoxicity of azoxystrobin - read-across to other strobilurins. OECD Environment, Health and Safety Publications Series on Testing and Assessment No. 327. ENV/JM/MONO(2020)23. - »Bioblast link«

S5.3

Betiu 2022 Int J Mol Sci CORRECTION.png
xx Bețiu AM, Noveanu L, Hâncu IM, Lascu A, Petrescu L, Maack C, Elmér E, Muntean DM (2022) Mitochondrial effects of common cardiovascular medications: the good, the bad and the mixed. Int J Mol Sci 23:13653. - »Bioblast link«

S5.3

Biner 2018 Chimia (Aarau) CORRECTION.png
xx Biner O, Schick T, Ganguin AA, von Ballmoos C (2018) Towards a synthetic mitochondrion. Chimia (Aarau) 72:291-6. - »Bioblast link«

S5.3

Black 2014 Antimicrob Agents Chemother CORRECTION.png
xx Black PA, Warren RM, Louw GE, van Helden PD, Victor TC, Kana BD (2014) Energy metabolism and drug efflux in Mycobacterium tuberculosis. Antimicrob Agents Chemother 58:2491-503. - »Bioblast link«

S5.3

Branca 2020 Front Cell Dev Biol CORRECTION.png
xx Branca JJV, Pacini A, Gulisano M, Taddei N, Fiorillo C, Becatti M (2020) Cadmium-induced cytotoxicity: effects on mitochondrial electron transport chain. Front Cell Dev Biol 8:604377. - »Bioblast link«

S5.3

Brandt 2013 Angew Chem Int Ed Engl CORRECTION.png
xx Brandt U (2013) Inside view of a giant proton pump. Angew Chem Int Ed Engl 52:7358-60. - »Bioblast link«

S5.3

Bratic 2013 J Clin Invest CORRECTION.png
xx Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123:951-7. - »Bioblast link«

S5.3

Cerqua 2021 Springer Cham CORRECTION.png
xx Cerqua C, Buson L, Trevisson E (2021) Mutations in assembly dactors required for the biogenesis of mitochondrial respiratory chain. Springer, Cham In: Navas P, Salviati L (eds) Mitochondrial diseases. - »Bioblast link«

S5.3

Curtabbi 2022 IUBMB Life CORRECTION.png
xx Curtabbi A, Enríquez JA (2022) The ins and outs of the flavin mononucleotide cofactor of respiratory complex I. IUBMB Life 74:629-44. - »Bioblast link«

S5.3

Distelmaier 2009 Brain CORRECTION.png
xx Distelmaier F, Koopman WJ, van den Heuvel LP, Rodenburg RJ, Mayatepek E, Willems PH, Smeitink JA (2009) Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 132:833-42. - »Bioblast link«

S5.3

Gasmi 2021 Arch Toxicol CORRECTION.png
xx 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. - »Bioblast link«

S5.3

Iqbal 2018 Pathogens CORRECTION.png
xx Iqbal IK, Bajeli S, Akela AK, Kumar A (2018) Bioenergetics of Mycobacterium: an emerging landscape for drug discovery. Pathogens 7:24. - »Bioblast link«

S5.3

Kim 2020 Cells CORRECTION.png
xx Kim J, Cheong JH (2020) Role of mitochondria-cytoskeleton interactions in the regulation of mitochondrial structure and function in cancer stem cells. Cells 9:1691. - »Bioblast link«

S5.3

Koene 2011 J Inherit Metab Dis CORRECTION.png
xx Koene S, Willems PH, Roestenberg P, Koopman WJ, Smeitink JA (2011) Mouse models for nuclear DNA-encoded mitochondrial complex I deficiency. J Inherit Metab Dis 34:293-307. - »Bioblast link«

S5.3

Lin 2013 PLoS One CORRECTION.png
xx Lin F, Chen Y, Levine R, Lee K, Yuan Y, Lin XN (2013) Improving fatty acid availability for bio-hydrocarbon production in Escherichia coli by metabolic engineering. PLoS One 8:e78595. - »Bioblast link«

S5.3

Maldonado 2022 Int J Mol Sci CORRECTION.png
xx Maldonado M, Abe KM, Letts JA (2022) A structural perspective on the RNA editing of plant respiratory Complexes. Int J Mol Sci 23:684. - »Bioblast link«

S5.3

Meyer 2022 New Phytol CORRECTION.png
xx Meyer EH, Letts JA, Maldonado M (2022) Structural insights into the assembly and the function of the plant oxidative phosphorylation system. New Phytol 235:1315-29. - »Bioblast link«

S5.3

Payen 2019 Cancer Metastasis Rev CORRECTION.png
xx Payen VL, Zampieri LX, Porporato PE, Sonveaux P (2019) Pro- and antitumor effects of mitochondrial reactive oxygen species. Cancer Metastasis Rev 38:189-203. - »Bioblast link«

S5.3

Penjweini 2020 Redox Biol CORRECTION.png
xx Penjweini R, Roarke B, Alspaugh G, Gevorgyan A, Andreoni A, Pasut A, Sackett DL, Knutson JR (2020) Single cell-based fluorescence lifetime imaging of intracellular oxygenation and metabolism. Redox Biol 34:101549. - »Bioblast link«
Labelling FAD as 'Free FAD' is incorrect, since the prosthetic group FAD/FADH2 remains covalently bound to the subunit SDHA of CII in the catalytic cycle.

S5.3

Puntel 2013 Toxicol In Vitro CORRECTION.png
xx 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«

S5.3

Sazanov 2015 Nat Rev Mol Cell Biol CORRECTION.png
xx Sazanov LA (2015) A giant molecular proton pump: structure and mechanism of respiratory complex I. Nat Rev Mol Cell Biol 16:375-88. - »Bioblast link«

S5.3

Schon 2018 Science CORRECTION.png
xx Schon EA (2018) Bioenergetics through thick and thin. Science 362:1114-5. - »Bioblast link«

S5.3

Srivastava 2016 Clin Transl Med CORRECTION.png
xx Srivastava S (2016) Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders. Clin Transl Med 5:25. - »Bioblast link«

S5.3

Toleikis 2020 Cells CORRECTION.png
xx 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«

S5.3

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

S5.3

Yang 2021 Springer CORRECTION.png
xx Yang Y, Wu Y, Sun XD, Zhang Y (2021) Reactive oxygen species, glucose metabolism, and lipid metabolism. Springer In: Huang C, Zhang Y (eds) Oxidative stress. Springer, Singapore. - »Bioblast link«
Fig. 9.1 Arrows are missing from substrates to products, which are required to make this graph meaningful.

S5.3


Supplement 6. NADH ⟶ NAD + H+ (+ e-)

NAD is the IUPAC symbol for nicotinamide adenine dinucleotide without implication of its oxidation state, whereas the oxidized form of NAD is NAD+ and the reduced form of NAD is NADH (in terms of total amount, NAD = NADH + NAD+).


6.1. NADH ⟶ NAD + H+ + e-

Chen 2022 Int J Mol Sci CORRECTION.png
xx 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«

S6.1

Lima 2021 Nat Metab CORRECTION.png
xx Lima A, Lubatti G, Burgstaller J, Hu D, Green AP, Di Gregorio A, Zawadzki T, Pernaute B, Mahammadov E, Perez-Montero S, Dore M, Sanchez JM, Bowling S, Sancho M, Kolbe T, Karimi MM, Carling D, Jones N, Srinivas S, Scialdone A, Rodriguez TA (2021) Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development. Nat Metab 3:1091-108. - »Bioblast link«

S6.1

Schniertshauer 2023 Curr Issues Mol Biol CORRECTION.jpg.png
xx 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«

S6.1


6.2. NADH ⟶ NAD + H+

Alston 2017 J Pathol CORRECTION.png
xx Alston CL, Rocha MC, Lax NZ, Turnbull DM, Taylor RW (2017) The genetics and pathology of mitochondrial disease. J Pathol 241:236-50. - »Bioblast link«

S6.2

Cuperus 2010 Cell Mol Life Sci CORRECTION.png
xx Cuperus R, Leen R, Tytgat GA, Caron HN, van Kuilenburg AB (2010) Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma. Cell Mol Life Sci 67:807-16. - »Bioblast link«

S6.2

Diaz 2023 Front Mol Biosci CORRECTION.png
xx 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«

S6.2

Jezek 2023 Antioxid Redox Signal CORRECTION.png
xx 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. https://doi.org/10.1089/ars.2022.0173 - »Bioblast link«

S6.2


Supplement 7. NADH ⟶ NAD+ + 2H+ (+ 2e-)

A bit of bioenergetic mystery is the origin of the form of the chemical reaction supposedly catalyzed by CI,
NADH → NAD+ + 2H+
If H+-linked electron transfer would be indicated, then the 2H+ should be directed together with 2e- to the prosthetic group FMN bound to CI instead of being pushed into the matrix space, and a H+ is missing on the substrate side. The unambiguous form of the equation is (Gnaiger 2023),
NADH + H+ → NAD+ + 2{H++e-}


7.1. NADH ⟶ NAD+ + 2H+ + 2e-

Anoar 2021 Front Neurosci CORRECTION.jpg
xx 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«

S7.1

Brischigliaro 2021 Biochim Biophys Acta Bioenerg CORRECTION.png
xx Brischigliaro M, Zeviani M (2021) Cytochrome c oxidase deficiency. Biochim Biophys Acta Bioenerg 1862:148335. - »Bioblast link«

S7.1

Chavda 2023 Antioxidants (Basel) CORRECTION.png
xx Chavda V, Lu B (2023) Reverse electron transport at mitochondrial Complex I in ischemic stroke, aging, and age-related diseases. Antioxidants (Basel) 12:895. - »Bioblast link«

S7.1

Cojocaru 2023 Antioxidants (Basel) CORRECTION.png
xx 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«

S7.1

Egan 2023 Physiol Rev CORRECTION.png
xx 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«

S7.1

Fahimi 2022 Trends in Chemistry CORRECTION.png
xx Fahimi P, Matta CF (2022) The hot mitochondrion paradox: reconciling theory and experiment. Trends in Chemistry 4:4-20. - »Bioblast link«
S7.1
Faria 2023 Pharmaceutics CORRECTION.png
xx Faria R, Boisguérin P, Sousa Â, Costa D (2023) Delivery systems for mitochondrial gene therapy: a review. Pharmaceutics 15:572. - »Bioblast link«

S7.1

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

S7.1

George 2023 Platelets CORRECTION.png
xx 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«

S7.1

Gopalakrishnan 2020 Sci Rep CORRECTION.png
xx 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«

S7.1

Hidalgo-Gutierrez CORRECTION.png
xx Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, Barriocanal-Casado E, López-Herrador S, Quinzii CM, López LC (2021) Metabolic targets of coenzyme Q10 in mitochondria. Antioxidants (Basel) 10:520. - »Bioblast link«

S7.1

Joshi 2022 Biomolecules CORRECTION.png
xx 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«

S7.1

Keidar 2023 Front Physiol CORRECTION.png
xx 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«

S7.1

Kobayashi 2023 Int J Mol Sci CORRECTION.png
xx Kobayashi A, Takeiwa T, Ikeda K, Inoue S (2023) Roles of noncoding RNAs in regulation of mitochondrial electron transport chain and oxidative phosphorylation. Int J Mol Sci 24:9414. - »Bioblast link«

S7.1

Kugler 2023 J Appl Physiol (1985) CORRECTION.png
xx Kugler BA, Thyfault JP, McCoin CS (2023) Sexually dimorphic hepatic mitochondrial adaptations to exercise: a mini-review. J Appl Physiol (1985) 134:685-91. - »Bioblast link«

S7.1

Lu 2023 Explor Res Hypothesis Med CORRECTION.png
xx 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«

S7.1

Martell 2023 Nat Commun CORRECTION.png
xx 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«

S7.1

Musicco 2023 Int J Mol Sci CORRECTION.png
xx Musicco C, Signorile A, Pesce V, Loguercio Polosa P, Cormio A (2023) Mitochondria deregulations in cancer offer several potential targets of therapeutic interventions. Int J Mol Sci 24:10420. - »Bioblast link«

S7.1

Nguyen 2021 Brief Bioinform CORRECTION.png
xx 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«

S7.1

Prasuhn 2021 Front Cell Dev Biol CORRECTION.png
xx 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«

S7.1

Shang 2023 Oncotarget CORRECTION.png
xx Shang E, Nguyen TTT, Westhoff MA, Karpel-Massler G, Siegelin MD (2023) Targeting cellular respiration as a therapeutic strategy in glioblastoma. Oncotarget 14:419-25. - »Bioblast link«

S7.1

Solhaug 2023 Cytotechnology CORRECTION.png
xx 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«

S7.1

Turton 2021 Expert Opinion Orphan Drugs CORRECTION.png
xx 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«

S7.1

Vargas-Mendoza 2021 Life (Basel) CORRECTION.png
xx 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«

S7.1

Vesga 2021 Med Chem Res CORRECTION.png
xx 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«

S7.1

Yang 2022 J Cleaner Production CORRECTION.png
xx 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«

S7.1

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

S7.1

7.2. NADH ⟶ NAD+ + 2H+ + e-

Gallinat 2022 Int J Mol Sci CORRECTION.png
xx 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«

S7.2

Ignatieva 2021 Int J Mol Sci CORRECTION.png
xx 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«

S7.2


7.3. NADH ⟶ NAD+ + 2H+

Dilliraj 2022 Nutrients CORRECTION.png
xx Dilliraj LN, Schiuma G, Lara D, Strazzabosco G, Clement J, Giovannini P, Trapella C, Narducci M, Rizzo R (2022) The evolution of ketosis: potential impact on clinical conditions. Nutrients 14:3613. - »Bioblast link«

S7.3

El-Gammal 2022 Pflugers Arch CORRECTION.png
xx El-Gammal Z, Nasr MA, Elmehrath AO, Salah RA, Saad SM, El-Badri N (2022) Regulation of mitochondrial temperature in health and disease. Pflugers Arch 474:1043-51. - »Bioblast link«

S7.3

Yu-Wai-Man 2011 Prog Retin Eye Res CORRECTION.png
xx Yu-Wai-Man P, Griffiths PG, Chinnery PF (2011) Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retin Eye Res 30:81-114. - »Bioblast link«

S7.3

Supplement 8. NADH ⟶ NAD + (2H+) + (2e-)

NAD is the IUPAC symbol for nicotinamide adenine dinucleotide without implication of its oxidation state, whereas the oxidized form of NAD is NAD+ and the reduced form of NAD is NADH (in terms of total amount, NAD = NADH + NAD+).


8.1. NADH ⟶ NAD + 2H+ + 2e-

Kataoka 2020 Microbiology Monographs CORRECTION.png
xx Kataoka N, Matsutani M, Matsushita K (2020) Respiratory chain and energy metabolism of Corynebacterium glutamicum. In: Inui M, Toyoda K (eds) Corynebacterium glutamicum. Microbiology Monographs 23. Springer, Cham. - »Bioblast link«

S8.1

Shields 2021 Front Cell Dev Biol CORRECTION.png
xx 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«

S8.1

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

S8.1


8.2. NADH ⟶ NAD + 2e-

Yang 2022 Front Cell Dev Biol CORRECTION.png
xx Yang J, Guo Q, Feng X, Liu Y, Zhou Y (2022) Mitochondrial dysfunction in cardiovascular diseases: potential targets for treatment. Front Cell Dev Biol 10:841523. - »Bioblast link«

S8.2


8.3. NADH ⟶ NAD + e-

Chi 2022 Biomedicines CORRECTION.png
xx Chi SC, Cheng HC, Wang AG (2022) Leber hereditary optic neuropathy: molecular pathophysiology and updates on gene therapy. Biomedicines 10:1930. - »Bioblast link«

S8.3

Geng 2023 Front Physiol CORRECTION.png
xx Geng Y, Hu Y, Zhang F, Tuo Y, Ge R, Bai Z (2023) Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets. Front Physiol 14:1239643. - »Bioblast link«

S8.3

Simon 2022 Function (Oxf) CORRECTION.png
xx Simon L, Molina PE (2022) Cellular bioenergetics: experimental evidence for alcohol-induced adaptations. Function (Oxf) 3:zqac039. - »Bioblast link«

S8.3


8.4. NADH ⟶ NAD

Beier 2015 FASEB J CORRECTION.png
xx Beier UH, Angelin A, Akimova T, Wang L, Liu Y, Xiao H, Koike MA, Hancock SA, Bhatti TR, Han R, Jiao J, Veasey SC, Sims CA, Baur JA, Wallace DC, Hancock WW (2015) Essential role of mitochondrial energy metabolism in Foxp3⁺ T-regulatory cell function and allograft survival. FASEB J 29:2315-26. - »Bioblast link«

S8.4

Howie 2014 Front Immunol CORRECTION.png
xx Howie D, Waldmann H, Cobbold S (2014) Nutrient sensing via mTOR in T cells maintains a tolerogenic microenvironment. Front Immunol 5:409. - »Bioblast link«

S8.4

Murray 2009 Genome Med CORRECTION.png
xx 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«

S8.4

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

S8.4

Steiner 2017 Int J Biochem Cell Biol CORRECTION.png
xx Steiner JL, Lang CH (2017) Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis. Int J Biochem Cell Biol 89:125-35. - »Bioblast link«

S8.4

Tirichen 2021 Front Physiol CORRECTION.png
xx Tirichen H, Yaigoub H, Xu W, Wu C, Li R, Li Y (2021) Mitochondrial reactive oxygen species and their contribution in chronic kidney disease progression through oxidative stress. Front Physiol 12:627837. - »Bioblast link«

S8.4

Wang 2021 Food Bioscience CORRECTION.png
xx Wang Peixin, Wang D, Hu J, Tan BK, Zhang Y, Lin S (2021) Natural bioactive peptides to beat exercise-induced fatigue: A review. Food Bioscience 43:101298. - »Bioblast link«

S8.4


Supplement 9. NADH + H+ ⟶ NAD + e-

Gopan 2021 World J Hepatol CORRECTION.png
xx Gopan A, Sarma MS (2021) Mitochondrial hepatopathy: Respiratory chain disorders- 'breathing in and out of the liver'. World J Hepatol 13:1707-26. - »Bioblast link«

S9


Supplement 10. NADH + H ⟶ NAD+ + 2e-

Vartak 2013 Protein Cell CORRECTION.png
xx Vartak R, Porras CA, Bai Y (2013) Respiratory supercomplexes: structure, function and assembly. Protein Cell 4:582-90. - »Bioblast link«
Fig. 1 of Vartak et al (2013): The misconstrued charge on FAD in FADH2 → FAD+ may explain the explicit one-electron (1e) transfer shown for the 2-electron transfer from FADH2.

S10

Supplement 11. NADH + H+ ⟶ NADH

Cadonic 2016 Mol Neurobiol CORRECTION.png
xx Cadonic C, Sabbir MG, Albensi BC (2016) Mechanisms of mitochondrial dysfunction in Alzheimer's disease. Mol Neurobiol 53:6078-90. - »Bioblast link«

S11


Supplement 12. NADH2 ⟶ NAD+

Papa 2007 Springer CORRECTION.png
xx Papa S, Petruzzella V, Scacco S (2007) Electron transport. Structure, redox-coupled protonmotive activity, and pathological disorders of respiratory chain Complexes. Springer, Boston, MA. In: Lajtha A, Gibson GE, Dienel GA (eds) Handbook of neurochemistry and molecular neurobiology:93–118. - »Bioblast link«

S12


Supplement 13. NADH ⟶ for CI, but NAD+ ⟶ NADH + H+ for TCA cycle DH

Dimauro 2009 Biochim Biophys Acta CORRECTION.png
xx DiMauro S, Rustin P (2009) A critical approach to the therapy of mitochondrial respiratory chain and oxidative phosphorylation diseases. Biochim Biophys Acta 1792:1159-67. - »Bioblast link«

S13


Supplement 14. Reverse

Grandoch 2019 Nat Metab CORRECTION.png
xx Grandoch M, Flögel U, Virtue S, Maier JK, Jelenik T, Kohlmorgen C, Feldmann K, Ostendorf Y, Castañeda TR, Zhou Z, Yamaguchi Y, Nascimento EBM, Sunkari VG, Goy C, Kinzig M, Sörgel F, Bollyky PL, Schrauwen P, Al-Hasani H, Roden M, Keipert S, Vidal-Puig A, Jastroch M5, Haendeler J, Fischer JW (2019) 4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue. Nat Metab 1:546-59. - »Bioblast link«
NADH is shown as the product of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequenty encountered when FADH2 is shown as the substrate of CII.

S14

Hunt 2018 PLoS Comput Biol CORRECTION.png
xx Hunt KA, Jennings RM, Inskeep WP, Carlson RP (2018) Multiscale analysis of autotroph-heterotroph interactions in a high-temperature microbial community. PLoS Comput Biol 14:e1006431. Nat Metab 1:546-59. - »Bioblast link«
NADH is shown as the product of the reaction catalyzed by CI in respiration.

S14

Zhao 2021 Mol Biomed CORRECTION.png
xx Zhao H, Li Y (2021) Cancer metabolism and intervention therapy. Mol Biomed 2:5. - »Bioblast link«

S14


Supplement 15. Cytochrome b6f Complex: NADP+ + H+ ⟶ NADPH

Baniulis 2008 Photochem Photobiol CORRECTION.png
xx Baniulis D, Yamashita E, Zhang H, Hasan SS, Cramer WA (2008) Structure-function of the cytochrome b6f complex. Photochem Photobiol 84:1349-58. - »Bioblast link«

S15

Hasan 2012 Phys Chem Chem Phys CORRECTION.png
xx Hasan SS, Cramer WA (2012) On rate limitations of electron transfer in the photosynthetic cytochrome b6f complex. Phys Chem Chem Phys 14:13853-60. - »Bioblast link«

S15

Liguori 2020 Photosynth Res CORRECTION.png
xx Liguori N, Croce R, Marrink SJ, Thallmair S (2020) Molecular dynamics simulations in photosynthesis. Photosynth Res 144:273-95. - »Bioblast link«

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Supplement 16. Other

Michelet 2013 Front Plant Sci CORRECTION.png
xx Michelet L, Zaffagnini M, Morisse S, Sparla F, Pérez-Pérez ME, Francia F, Danon A, Marchand CH, Fermani S, Trost P, Lemaire SD (2013) Redox regulation of the Calvin-Benson cycle: something old, something new. Front Plant Sci 4:470. - »Bioblast link«

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xx Lauterbach L, Lenz O, Vincent KA (2013) H₂-driven cofactor regeneration with NAD(P)⁺-reducing hydrogenases. FEBS J 280:3058-68. - »Bioblast link«

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xx Li F, Hinderberger J, Seedorf H, Zhang J, Buckel W, Thauer RK (2008) Coupled ferredoxin and crotonyl coenzyme A (CoA) reduction with NADH catalyzed by the butyryl-CoA dehydrogenase/Etf complex from Clostridium kluyveri. J Bacteriol 190:843-50. - »Bioblast link«

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xx Reeve HA, Lauterbach L, Lenz O, Vincent KA (2015) Enzyme-modified particles for selective biocatalytic hydrogenation by hydrogen-driven NADH recycling. ChemCatChem 7:3480-7. - »Bioblast link«

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XX Liang J, Huang H, Wang S (2019) Distribution, evolution, catalytic mechanism, and physiological functions of the flavin-based electron-bifurcating NADH-dependent reduced ferredoxin: NADP+ oxidoreductase. Front Microbiol 10:373. - »Bioblast link«

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Subcategories

This category has the following 3 subcategories, out of 3 total.

Pages in category "Ambiguity crisis - NAD and H+"

The following 180 pages are in this category, out of 180 total.

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