Validating the predictions of murburn model for oxygenic photosynthesis: Analyses of ligand-binding to protein complexes and cross-system comparisons

Manoj, Kelath Murali; Gideon, Daniel Andrew; Parashar, Abhinav; Nirusimhan, Vijay; Annadurai, Pushparaj; Jacob, Vivian David; Manekkathodi, Afsal

doi:10.1080/07391102.2021.1953607

Cited by 22 publications

(33 citation statements)

References 205 publications

(33 reference statements)

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“…To date, murburn concept-based de novo explanations were provided for diverse fundamental aspects of life: moiety and electron transfers mediated by heme-/flavin-enzymes (Andrew et al, 2012;Gideon et al, 2021;Manoj, 2006;Manoj & Hager, 2008;Manoj et al, 2010;Parashar et al, 2014;, aerobic respiration Manoj, Soman, et al, 2019;, oxygenic photosynthesis (Gideon et al, 2020;Manoj, Gideon, Parashar, Nirusimhan, et al, 2021), xenobiotic metabolism , idiosyncratic/hormetic dose responses (Parashar et al, 2018), homeostasis/TMP/thermogenesis Manoj et al, 2018), signal transduction in vision , explanations for hemoglobin's role as an ATP-synthase in erythrocytes , and so forth.…”

Section: What Are the Major Perceptional Changes That Murburn Concept Ushers In?mentioning

confidence: 99%

The murburn precepts for cellular ionic homeostasis and electrophysiology

Manoj¹,

Bazhin

Tamagawa

2021

Journal Cellular Physiology

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Starting from basic molecular structure and redox properties of its components, we build a macroscopic cellular electrophysiological model. We first present a murburn purview that could explain ion-distribution in bulk-milieu/membrane-interface and support the origin of transmembrane potential (TMP) in cells. In particular, the discussion focuses on how cells achieve disparity in the distribution of monovalent and divalent cations within (K + > Na + > Mg 2+ > Ca 2+ ) and outside (Na + > K + > Ca 2+ > Mg 2+ ). We explore how TMP could vary for resting/graded/action potentials generation and project a model for impulse conduction in neurons. Outcomes based in murburn bioenergetic equilibriums leading to solubilization of ionpairs, membrane's permittivity, protein channels' fluxes, and proteins' innate ability to bind/adsorb ions selectively are projected as the integral rationale. We also provide experimental modalities to ratify the projections.

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Section: What Are the Major Perceptional Changes That Murburn Concept Ushers In?mentioning

confidence: 99%

The murburn precepts for cellular ionic homeostasis and electrophysiology

Manoj¹,

Bazhin

Tamagawa

2021

Journal Cellular Physiology

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“…It would be wrong not to consider the arguments given here within this broader context (though each argument merits to be critically evaluated on its own). The murburn hypothesis is a new broad concept giving simple, thermodynamically and kinetically feasible explanations to the theoretical and experimental findings in several other systems, like substrate diversities or selectivity of peroxidases 48 or cytochrome P450s, 49,50 unusual physiological dose responses, 51 aerobic respiration, 2 oxygenic photosynthesis, 28,29 ionic differentials and electrophysiology, 52 physiology of vision, 53 etc. Clearly, it can be seen that murburn purview spans the entire spectrum of redox physiological activity at diverse loci in and out of cells, and is not just confined to bioenergetic phosphorylations 29,54 .…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that the CBCs and other pertinent membrane complexes in mitochondria/chloroplasts do not have the structural capacity to differentiate the various quinones/quinols, to enable them a kinetically and mechanistically viable docking at their purported sites. 27,29 A visual examination of the head group structures of naturally occurring quinones is presented in Figure 4. The dimensions and the substitutions on the head/tail groups vary considerably and combinations of such quinols are present in various organisms.…”

Section: Is the Q-cycle Necessary For Oxphos Or Photophos Routines?mentioning

confidence: 99%

“…Clearly, it can be seen that murburn purview spans the entire spectrum of redox physiological activity at diverse loci in and out of cells, and is not just confined to bioenergetic phosphorylations. 29,54 In our earlier studies on the particular topic of focus, we had demonstrated some of the mechanistically untenable aspects of Q-cycle 3 and explored the experimental/structural aspects of interactive dynamics with proteins like cytochrome c. 30,55 In the current analytical exploration, we have investigated various theoretical and structural aspects of diverse membrane-embedded proteins that interact with the spectrum of quinones/quinols in bioenergetically important membranes. In particular, we explored the feasibility for the conservation of 'free energy landscapes' as modelled by Yuly et al 7 and investigated the structural features that could enable a deterministic electron routing within the membrane protein complexes.…”

Section: Is the Q-cycle Necessary For Oxphos Or Photophos Routines?mentioning

confidence: 99%

“…Several aspects of the CRAS proposal have been questioned over decades by very seasoned scientists 26 . Recently, the ETC‐CRAS ideas were demonstrated to be an untenable and redundant concept, as seen from a multitude of perspectives 2,3,26‐30 . Advocates of CRAS have periodically changed the original proposals in the light of criticism and this cannot be a saving grace for its untenable assumptions and explanations.…”

Section: Fundamental Queries and Deductions Based On Available Datamentioning

confidence: 99%

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Interaction of membrane‐embedded cytochrome b‐complexes with quinols: Classical Q‐cycle and murburn model

Manoj¹,

Gideon²,

Jaeken

2022

Cell Biochemistry & Function

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We recently proposed a diffusible reactive (oxygen) species (DRS/DROS) based function for cytochrome b complexes (CBC) and quinones (Q)/quinols (QH2) in the murburn model of bioenergetics. This proposal is in direct conflict with the classical purview of Q‐cycle. Via extensive analyses of the structure‐function correlations of membrane‐quinones/quinols and proteins, we present qualitative and quantitative arguments to infer that the classical model cannot explain the energetics, kinetics, mechanism and probabilistic considerations. Therefore, it is proposed that Q‐cycle is neither necessary nor feasible at CBCs. In contrast, we substantiate that the murburn model explains: (a) crucial structural data of CBCs, (b) why quinones/quinols are utilized in bioenergetic membranes, (c) how trans‐membrane potential is generated owing to effective charge separation at CBCs, (d) mobility data of O2, DRS, Q/QH2, and (e) utility of other reaction/membrane components. Further, the murburn model also accommodates the absence of quinones in anaerobic Archaea, wherein methanophenazines are prevalent. The work mandates that the textbooks and research agendas are refreshed to reflect the new perception. Significance The current article must be seen as a critical and detailed analysis of the role and working mechanism of quinone (Q) /quinols (QH2) in bioenergetic membranes. In the classical model, QH2 are perceived as highly mobile electron‐transport agents that bind and donate electrons to cytochrome b complexes (CBCs), using sophisticated electronic circuitries, in order to recycle Q and pump protons. The classical perception sees radicals (such as Q*‐, O2*‐, etc., also called diffusible reactive species, DRS) as wasteful or toxic (patho) physiological manifestations. It is highlighted herein that QH2 has low mobility and matrix has little protons to pump. New insights from the structural analyses of diverse CBCs and quinols, in conjunction with murburn reaction thermodynamics suggest that the electrons from substrates/quinols are effectively utilized via DRS. This perception fits into a much broader analysis of 1 and 2 electron transfers in overall redox metabolism, as recently brought out by the murburn model, wherein DRS are considered obligatory ingredients of physiology. Thus, the findings mandate a reorientation in the pertinent research field.

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Why do cells need oxygen? Insights from mitochondrial composition and function

Manoj¹,

Gideon²,

Jaeken

2021

Cell Biology International

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Mitochondrial membrane‐embedded redox proteins are classically perceived as deterministic “electron transport chain” (ETC) arrays cum proton pumps; and oxygen is seen as an “immobile terminal electron acceptor.” This is untenable because: (1) there are little free protons to be pumped out of the matrix; (2) proton pumping would be highly endergonic; (3) ETC‐chemiosmosis‐rotary ATP synthesis proposal is “irreducibly complex”/”non‐evolvable” and does not fit with mitochondrial architecture or structural/distribution data of the concerned proteins/components; (4) a plethora of experimental observations do not conform to the postulates/requisites; for example, there is little evidence for viable proton‐pumps/pH‐gradient in mitochondria, trans‐membrane potential (TMP) is non‐fluctuating/non‐trappable, oxygen is seen to give copious “diffusible reactive (oxygen) species” (DRS/DROS) in milieu, etc. Quite contrarily, the newly proposed murburn model's tenets agree with known principles of energetics/kinetics, and builds on established structural data and reported observations. In this purview, oxygen is needed to make DRS, the principal component of mitochondrial function. Complex V and porins respectively serve as proton‐inlet and turgor‐based water‐exodus portals, thereby achieving organellar homeostasis. Complexes I to IV possess ADP‐binding sites and their redox‐centers react/interact with O2/DRS. At/around these complexes, DRS cross‐react or activate/oxidize ADP/Pi via fast thermogenic one‐electron reaction(s), condensing to form two‐electron stabilized products (H2O2/H2O/ATP). The varied architecture and distribution of components in mitochondria validate DRS as (i) the coupling agent of oxidative reactions and phosphorylations, and (ii) the primary reason for manifestation of TMP in steady‐state. Explorations along the new precepts stand to provide greater insights on mitochondrial function and pathophysiology.

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Validating the predictions of murburn model for oxygenic photosynthesis: Analyses of ligand-binding to protein complexes and cross-system comparisons

Cited by 22 publications

References 205 publications

The murburn precepts for cellular ionic homeostasis and electrophysiology

The murburn precepts for cellular ionic homeostasis and electrophysiology

Interaction of membrane‐embedded cytochrome b‐complexes with quinols: Classical Q‐cycle and murburn model

Why do cells need oxygen? Insights from mitochondrial composition and function

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