Difference between revisions of "Ambiguity crisis"
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|description= | |description=The '''ambiguity crisis''' is a contemporary crisis comparable to the credibility or [[reproducibility crisis]]. The term 'crisis' is rooted etymologically in the Greek word ''krinein'': meaning to 'separate, decide, judge'. In this sense, science and communication in general are a continuous crisis at the edge of separating clarity or certainty from confusing double meaning, or obscure 'alchemical' gibberish, or even fake-news. Reproducibility relates to the condition of repeating and confirming calculations or experiments presented in a published resource. While ambiguity is linked to relevant issues of reproducibility, it extends to the communications space of terminological and graphical representations of concepts. Type 1 ambiguities are the inevitable consequence of conceptual evolution, in the process of which ambiguities are replaced by experimentally and theoretically supported paradigm shifts to clear-cut theorems. In contrast, type 2 ambiguities are traced in publications that reflect merely a disregard and ignorance of established concepts without an attempt to justify the inherent deviations from high-quality science. There are many shades of grey between these types of ambiguity. | ||
|info=Gnaiger E (2023) Complex II ambiguities ― FADH<sub>2</sub> in the electron transfer system. J Biol Chem. https://doi.org/10.1016/j.jbc.2023.105470 | |info=Gnaiger E (2023) Complex II ambiguities ― FADH<sub>2</sub> in the electron transfer system. J Biol Chem. https://doi.org/10.1016/j.jbc.2023.105470 | ||
}} | }} | ||
Revision as of 00:02, 28 November 2023
- high-resolution terminology - matching measurements at high-resolution
Ambiguity crisis
Description
The ambiguity crisis is a contemporary crisis comparable to the credibility or reproducibility crisis. The term 'crisis' is rooted etymologically in the Greek word krinein: meaning to 'separate, decide, judge'. In this sense, science and communication in general are a continuous crisis at the edge of separating clarity or certainty from confusing double meaning, or obscure 'alchemical' gibberish, or even fake-news. Reproducibility relates to the condition of repeating and confirming calculations or experiments presented in a published resource. While ambiguity is linked to relevant issues of reproducibility, it extends to the communications space of terminological and graphical representations of concepts. Type 1 ambiguities are the inevitable consequence of conceptual evolution, in the process of which ambiguities are replaced by experimentally and theoretically supported paradigm shifts to clear-cut theorems. In contrast, type 2 ambiguities are traced in publications that reflect merely a disregard and ignorance of established concepts without an attempt to justify the inherent deviations from high-quality science. There are many shades of grey between these types of ambiguity.
Reference: Gnaiger E (2023) Complex II ambiguities ― FADH2 in the electron transfer system. J Biol Chem. https://doi.org/10.1016/j.jbc.2023.105470
- Complex II ambiguities (Gnaiger 2023): The prosthetic group FADH2 appears erroneously as the substrate of CII in the ETS linked to succinate oxidation in many publications (2001 to 2023) and numerous educational websites (Gnaiger 2023b). In fact, the succinate dehydrogenase - synonymous with CII - oxidizes succinate and reduces the covalently bound prosthetic group FAD to FADH2 in the canonical forward tricarboxylic acid cycle at the entry to the membrane-bound ETS with further electron transfer into the Q-junction.
- The elusive chemical proton (Complex I and hydrogen ion ambiguities in the electron transfer system): The current literature contains inconsistencies regarding H+ formation on 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.
- Oxidative stress (Azzi 2022): A prominent case of ambiguity in the grey zone between types 1 and 2 has been uniquely demonstrated by analysis of the popular notion of 'oxidative stress' - a term more frequently found in PubMed than 'mitochondria', widely used with vague definition and without expression by numerical values and corresponding units.
- Normoxia and hypoxia (Donnelly et al 2022): Anthropocentric and clinical perspectives on hypoxia clash with an evolutionary view of life in environments of different oxygen regimes. Microenvironmental oxygenation is in stark contrast to the ambient oxygen level in our macroscopic environment, which we often apply uncritically in studies with isolated mitochondria or cultured cells, when ambient normoxia implies effectively hyperoxic experimental conditions.
- The force-pressure ambiguity (Gnaiger 2020 Chapter 8): The ambiguous use (type 1) of the terms force and pressure has deep consequences on the enigmatic concept of non-ohmic flux-force relationships in the context of mitochondrial membrane potential and the protonmotive force.
- Uncoupling, decoupling, dyscoupling (Gnaiger et al 2020 Section 2.4): Rigorous definition is warranted.
- Respiratory State 2 - ROX or LEAK? (Gnaiger et al 2020 Section 2.6.2): Rigorous definition is warranted with reference to the original definition by Chance, Williams 1955).
- Respiratory State 3 - high or saturating [ADP]? (Gnaiger et al 2020 Section 2.6.3): Rigorous definition is warranted where the OXPHOS state is distinguished from State 3 as originally defined by Chance, Williams 1955).
- Negative entropy (Negative entropy for living systems: controversy between nobel laureates Schrödinger, Pauling and Perutz): 'Entropy is a simple and clear concept, whereas discussing about entropy is not simple and not always clear. I leave this to Wittgenstein for comment.'
Correction: FADH2 and Complex II
- FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
- 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 - »Bioblast link«
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.
- 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.
- 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.
- 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.
References
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