The Experts below are selected from a list of 369 Experts worldwide ranked by ideXlab platform
Kelath Murali Manoj - One of the best experts on this subject based on the ideXlab platform.
-
Rebutting Pedro J. Silva’s article in Biophysical Chemistry supporting Mitchell-Boyer’s ideas on bioenergetics and advocating murburn concept as a viable explanation for aerobic respiration and oxygenic photosynthesis
2020Co-Authors: Kelath Murali ManojAbstract:Over the last three years, I had pointed out the untenable nature of the proton-centric ‘Chemiosmosis driven rotary ATP-synthesis (CRAS)’ explanation for Oxidative Phosphorylation (OxPhos). Recently, Pedro J. Silva (PJS) [Chemiosmotic misunderstandings (2020). Biophys. Chem. 264, 106424] afforded a part of our work his critical attention, but overlooked the large volume of evidence against CRAS and supporting the oxygen-centric murburn mechanism of OxPhos. In his article, PJS also posed some queries on our bioenergetics model. When I offered my rebuttal, the Editor of Biophysical Chemistry refused to publish it. Therefore, I have no other option than to publish the rebuttal as a preprint. Herein, I demonstrate the flaws and lacunae in PJS’s defense of CRAS hypothesis and answer his specific queries and defend the murburn explanation of mOxPhos. The current scientific discourse is crucial for correcting major historical errors in mitochondrial physiology and understanding oxygen’s crucial role in the powering chemistry of life.
-
Chemiosmotic and murburn explanations for aerobic respiration: Predictive capabilities, structure-function correlations and chemico-physical logic.
Archives of biochemistry and biophysics, 2019Co-Authors: Kelath Murali Manoj, Vidhu Soman, Vivian David Jacob, Abhinav Parashar, Daniel Andrew Gideon, Manish Kumar, Afsal Manekkathodi, Surjith Ramasamy, Kannan Pakshirajan, Nikolai M. BazhinAbstract:Abstract Since mid-1970s, the proton-centric proposal of ‘Chemiosmosis’ became the acclaimed explanation for aerobic respiration. Recently, significant theoretical and experimental evidence were presented for an oxygen-centric ‘murburn’ mechanism of mitochondrial ATP-synthesis. Herein, we compare the predictive capabilities of the two models with respect to the available information on mitochondrial reaction chemistry and the membrane proteins' structure-function correlations. Next, fundamental queries are addressed on thermodynamics of mitochondrial oxidative phosphorylation (mOxPhos): (1) Can the energy of oxygen reduction be utilized for proton transport? (2) Is the trans-membrane proton differential harness-able as a potential energy capable of doing useful work? and (3) Whether the movement of miniscule amounts of mitochondrial protons could give rise to a potential of ~200 mV and if such an electrical energy could sponsor ATP-synthesis. Further, we explore critically if rotary ATPsynthase activity of Complex V can account for physiological ATP-turnovers. We also answer the question- “What is the role of protons in the oxygen-centric murburn scheme of aerobic respiration?” Finally, it is demonstrated that the murburn reaction model explains the fast kinetics, non-integral stoichiometry and high yield of mOxPhos. Strategies are charted to further demarcate the two explanations' relevance in the cellular physiology of aerobic respiration.
-
Chemiosmosis principle versus murburn concept: Why do cells need oxygen? Deducing the underpinnings of aerobic respiration by mechanistic predictability
2019Co-Authors: Kelath Murali Manoj, Vidhu Soman, Vivian David Jacob, Abhinav Parashar, Daniel Andrew Gideon, Manish Kumar, Afsal Manekkathodi, Surjith Ramasamy, Kannan PakshirajanAbstract:The long-standing explanation for cellular respiration (mitochondrial oxidative phosphorylation, mOxPhos) in textbooks is proton-centric and involves the elements of Rotary ATP synthesis, Chemiosmosis principle, Proton pumps and Electron transport chain (in short, the RCPE model). Addressing certain lacunae in the RCPE model, an alternative scheme based on murburn concept was proposed in 2017 (Manoj, 2017). The new proposal is oxygen-centric in essence, and it advocates constructive roles for diffusible reactive oxygen species (DROS) in electron transfer reactions and ATP-synthesis. By the end of 2018, significant arguments and experimental evidences (in vitro, in situ, and in silico) had accumulated supporting the new mechanism. Herein, the authors compare the predictive capabilities of the two models. Theoretical concepts and expectations are detailed to differentiate the two models, and the correlations are cross-checked with the available data/information. Experimental strategies are further charted to delineate and demarcate the two hypotheses’ relevance in mOxPhos.
-
2020: murburn concept heralds a new era in cellular bioenergetics
Biomedical Reviews, 2019Co-Authors: Daniel Andrew Gideon, Vivian David Jacob, Kelath Murali ManojAbstract:Cellular bioenergetics has been interpreted for several decades using the Keilin-Mitchell-Boyer (KMB) model of oxidative phosphorylation (OxPhos), and for understanding/managing of the pertinent mitochondrial pathophysiological states. Although decades of research had revealed many faulty chemico-physical aspects of KMB perspective, recent critical insights from our group’s writings have sufficiently brought out the errors in the KMB model, rendering it obsolete/redundant. The murburn model proposed in lieu is a compelling alternative for explaining OxPhos because it reasons several facets of mitochondrial structure-function correlations, reaction chemistry and thermodynamics. However, the mitochondrial research community appears to be recalcitrant, and continues to follow the erstwhile erroneous ideas and not take cognizance of the new insights. Hence, we deemed it opportune to make a clarion call for a jettisoning of the superseded terminologies (or keywords) and concepts routinely used by researchers in this field. First, we present a statistical perspective of the usage of these terms in the past and recent times, to support our claims and call. Then, we articulate simplified arguments why the key elements/terms of the KMB model like “electron-transfer/electron-transport/respiratory chain”, “mitochondrial proton pumps”, “mitochondrial membrane po-tential”, “Chemiosmosis”, “proton motive force” and “rotary ATP synthase/synthesis” violate scientific/semantic logic. Finally, we conclude with summative statements projecting the importance of our claims and call.
-
Aerobic Respiration: Criticism of the Proton-centric Explanation Involving Rotary Adenosine Triphosphate Synthesis, Chemiosmosis Principle, Proton Pumps and Electron Transport Chain.
Biochemistry insights, 2018Co-Authors: Kelath Murali ManojAbstract:The acclaimed explanation for mitochondrial oxidative phosphorylation (mOxPhos, or cellular respiration) is a deterministic proton-centric scheme involving four components: Rotary adenosine triphos...
John S. Torday - One of the best experts on this subject based on the ideXlab platform.
-
Quantum Mechanics predicts evolutionary biology.
Progress in biophysics and molecular biology, 2018Co-Authors: John S. TordayAbstract:Abstract Nowhere are the shortcomings of conventional descriptive biology more evident than in the literature on Quantum Biology. In the on-going effort to apply Quantum Mechanics to evolutionary biology, merging Quantum Mechanics with the fundamentals of evolution as the First Principles of Physiology-namely negentropy, Chemiosmosis and homeostasis-offers an authentic opportunity to understand how and why physics constitutes the basic principles of biology. Negentropy and Chemiosmosis confer determinism on the unicell, whereas homeostasis constitutes Free Will because it offers a probabilistic range of physiologic set points. Similarly, on this basis several principles of Quantum Mechanics also apply directly to biology. The Pauli Exclusion Principle is both deterministic and probabilistic, whereas non-localization and the Heisenberg Uncertainty Principle are both probabilistic, providing the long-sought after ontologic and causal continuum from physics to biology and evolution as the holistic integration recognized as consciousness for the first time.
-
The resolution of ambiguity as the basis for life: A cellular bridge between Western reductionism and Eastern holism.
Progress in biophysics and molecular biology, 2017Co-Authors: John S. Torday, William B. MillerAbstract:Boundary conditions enable cellular life through negentropy, Chemiosmosis, and homeostasis as identifiable First Principles of Physiology. Self-referential awareness of status arises from this organized state to sustain homeostatic imperatives. Preferred homeostatic status is dependent upon the appraisal of information and its communication. However, among living entities, sources of information and their dissemination are always imprecise. Consequently, living systems exist within an innate state of ambiguity. It is presented that cellular life and evolutionary development are a self-organizing cellular response to uncertainty in iterative conformity with its basal initiating parameters. Viewing the life circumstance in this manner permits a reasoned unification between Western rational reductionism and Eastern holism.
-
Life Is Simple—Biologic Complexity Is an Epiphenomenon
Biology, 2016Co-Authors: John S. TordayAbstract:Life originated from unicellular organisms by circumventing the Second Law of Thermodynamics using the First Principles of Physiology, namely negentropy, Chemiosmosis and homeostatic regulation of calcium and lipids. It is hypothesized that multicellular organisms are merely contrivances or tools, used by unicellular organisms as agents for the acquisition of epigenetic inheritance. The First Principles of Physiology, which initially evolved in unicellular organisms are the exapted constraints that maintain, sustain and perpetuate that process. To ensure fidelity to this mechanism, we must return to the first principles of the unicellular state as the determinants of the primary level of selection pressure during the life cycle. The power of this approach is reflected by examples of its predictive value. This perspective on life is a "game changer", mechanistically rendering transparent many dogmas, teleologies and tautologies that constrain the current descriptive view of Biology.
Richard A. Dilley - One of the best experts on this subject based on the ideXlab platform.
-
On Why Thylakoids Energize ATP Formation Using Either Delocalized or Localized Proton Gradients – A Ca^2+ Mediated Role in Thylakoid Stress Responses
Photosynthesis Research, 2004Co-Authors: Richard A. DilleyAbstract:By the early 1970s, the chemiosmotic hypothesis of Peter Mitchell was widely accepted by bioenergetics researchers as the best conceptual scheme to explain how ATP is formed in oxidative and photosynthetic phosphorylation. At about the same time, however, work from a few laboratories suggested that some aspects of that elegant, relatively simple hypothesis required revision – not abandonment, but refinement to accommodate more complex movements of protons in the ATP formation mechanism than originally envisioned by Peter Mitchell. In some situations it appeared that protons were constrained to localized domains rather than always delocalized within an enclosed vesicle as envisioned by Chemiosmosis. This minireview tells that story from my perspective, as one of the researchers involved in the experimental approaches that revealed more complex energy coupling proton flux patterns. Ionic conditions during isolated thylakoid storage were found to reversibly switch the $$\Delta \tilde \mu _{{\text{H}}^{\text{ + }} } $$ gradient driving ATP formation between delocalized and localized energy coupling modes. Thylakoid accessible Ca^2+ ions proved to be the switching factor that was responding to the ionic conditions in the storage treatment. The mechanism of Ca^2+ was at least partially demystified when it was shown that the reversible switching between $$\Delta \tilde \mu _{{\text{H}}^{\text{ + }} } $$ energy coupling modes involved Ca^2+ interactions with the 8 kDa CF_0 (the H^+ channel) subunit in a type of H^+ flux gating action. Other experiments showed that the Ca^2+ gating of H^+ flux into the lumen may be a critical regulatory factor in controlling the lumen pH and thereby help regulate the activity of the violaxanthin de-epoxidase enzyme, a key part of the chloroplast photoprotective response to over-energization (excess light) stress.
-
On why thylakoids energize ATP formation using either delocalized or localized proton gradients - a ca(2+) mediated role in thylakoid stress responses.
Photosynthesis research, 2004Co-Authors: Richard A. DilleyAbstract:By the early 1970s, the chemiosmotic hypothesis of Peter Mitchell was widely accepted by bioenergetics researchers as the best conceptual scheme to explain how ATP is formed in oxidative and photosynthetic phosphorylation. At about the same time, however, work from a few laboratories suggested that some aspects of that elegant, relatively simple hypothesis required revision - not abandonment, but refinement to accommodate more complex movements of protons in the ATP formation mechanism than originally envisioned by Peter Mitchell. In some situations it appeared that protons were constrained to localized domains rather than always delocalized within an enclosed vesicle as envisioned by Chemiosmosis. This minireview tells that story from my perspective, as one of the researchers involved in the experimental approaches that revealed more complex energy coupling proton flux patterns. Ionic conditions during isolated thylakoid storage were found to reversibly switch the [Formula: see text] gradient driving ATP formation between delocalized and localized energy coupling modes. Thylakoid accessible Ca(2+) ions proved to be the switching factor that was responding to the ionic conditions in the storage treatment. The mechanism of Ca(2+) was at least partially demystified when it was shown that the reversible switching between [Formula: see text] energy coupling modes involved Ca(2+) interactions with the 8 kDa CF(0) (the H(+) channel) subunit in a type of H(+) flux gating action. Other experiments showed that the Ca(2+) gating of H(+) flux into the lumen may be a critical regulatory factor in controlling the lumen pH and thereby help regulate the activity of the violaxanthin de-epoxidase enzyme, a key part of the chloroplast photoprotective response to over-energization (excess light) stress.
-
On why thylakoids energize ATP formation using either delocalized or localized proton gradients - a ca(2+) mediated role in thylakoid stress responses.
Photosynthesis Research, 2004Co-Authors: Richard A. DilleyAbstract:By the early 1970s, the chemiosmotic hypothesis of Peter Mitchell was widely accepted by bioenergetics researchers as the best conceptual scheme to explain how ATP is formed in oxidative and photosynthetic phosphorylation. At about the same time, however, work from a few laboratories suggested that some aspects of that elegant, relatively simple hypothesis required revision — not abandonment, but refinement to accommodate more complex movements of protons in the ATP formation mechanism than originally envisioned by Peter Mitchell. In some situations it appeared that protons were constrained to localized domains rather than always delocalized within an enclosed vesicle as envisioned by Chemiosmosis. This minireview tells that story from my perspective, as one of the researchers involved in the experimental approaches that revealed more complex energy coupling proton flux patterns. Ionic conditions during isolated thylakoid storage were found to reversibly switch the \( \Delta \tilde \mu _{H^ + } \) gradient driving ATP formation between delocalized and localized energy coupling modes. Thylakoid accessible Ca2+ ions proved to be the switching factor that was responding to the ionic conditions in the storage treatment. The mechanism of Ca2+ was at least partially demystified when it was shown that the reversible switching between \( \Delta \tilde \mu _{H^ + } \) energy coupling modes involved Ca2+ interactions with the 8 kDa CF0 (the H+ channel) subunit in a type of H+ flux gating action. Other experiments showed that the Ca2+ gating of H+ flux into the lumen may be a critical regulatory factor in controlling the lumen pH and thereby help regulate the activity of the violaxanthin de-epoxidase enzyme, a key part of the chloroplast photoprotective response to over-energization (excess light) stress.
Sunil Nath - One of the best experts on this subject based on the ideXlab platform.
-
Molecular-level understanding of biological energy coupling and transduction: Response to “Chemiosmotic misunderstandings”
Biophysical chemistry, 2020Co-Authors: Sunil NathAbstract:Abstract In a recent paper entitled “Chemiosmotic misunderstandings”, it is claimed that “enough shortcomings in Mitchell's chemiosmotic theory have not been found and that a novel paradigm that offers at least as much explanatory power as Chemiosmosis is not ready.” This view is refuted by a wealth of molecular-level experimental data and strong new theoretical and computational evidence. It is shown that the chemiosmotic theory was beset with a large number of major shortcomings ever since the time when it was first proposed in the 1960s. These multiple shortcomings and flaws of Chemiosmosis were repeatedly pointed out in incisive critiques by biochemical authorities of the late 20th century. All the shortcomings and flaws have been shown to be rectified by a quantitative, unified molecular-level theory that leads to a deeper and far more accurate understanding of biological energy coupling and ATP synthesis. The new theory is shown to be consistent with pioneering X-ray and cryo-EM structures and validated by state-of-the-art single-molecule techniques. Several new biochemical experimental tests are proposed and constructive ways for providing a revitalizing conceptual background and theory for integration of the available experimental information are suggested.
-
Modern theory of energy coupling and ATP synthesis. Violation of Gauss's law by the chemiosmotic theory and validation of the two-ion theory.
Biophysical chemistry, 2019Co-Authors: Sunil NathAbstract:Abstract Adenosine triphosphate (ATP) is the universal biological energy fuel, or nature’s gasoline. The vast quantities of ATP required for sustenance of living processes in cells are synthesized by oxidative phosphorylation and photosynthesis. The chemiosmotic theory of energy coupling was proposed by Mitchell more than 50 years ago but has a contentious history. Part of the accumulated body of experimental evidence supports Mitchell’s theory, and part of the evidence conflicts with the theory. Although Mitchell’s theory was strongly criticized by several prominent scientists, the controversy was never resolved. Certain theoretical arguments and electrostatic calculations were originally made to justify the central tenet of the chemiosmotic theory of electrogenic proton transfer and violation of electrical neutrality in bulk aqueous phases by creation of a delocalized field. However, these calculations have not been scientifically scrutinized previously. Here it is proved from first principles that the original physical arguments and calculations made in support of steady state electrogenic ion transfer and Chemiosmosis violate Gauss’s law. Nath’s two-ion theory of energy coupling in which the field is local, and ion translocation is dynamically electrogenic but overall electroneutral is shown to satisfactorily resolve the difficulties. Characterization of length scales in mitochondrial systems is shown to impose strong constraints on possible mechanisms of energy transduction. Some biological implications for energy coupling, transduction and ATP synthesis arising as a result of the above analysis are discussed. Examples of several other biological processes where the new theory is useful such as apoptosis, muscle contraction, the joint multisite regulation of oxidative phosphorylation and the Krebs cycle, and hindered protein aggregation arising from ATP’s hydrotropic properties are outlined.
Kiriakos Kotzabasis - One of the best experts on this subject based on the ideXlab platform.
-
The Over-expression of the Plastidial Transglutaminase from Maize in Arabidopsis Increases the Activation Threshold of Photoprotection
Frontiers in Plant Science, 2016Co-Authors: Nikolaos E. Ioannidis, Dimitris Malliarakis, Josep María Torné, Mireya Santos, Kiriakos KotzabasisAbstract:Plastidial transglutaminase is one of the most promising enzymes in chloroplast bioenergetics due to its link with polyamine pathways and the cross talk with signals such as Ca+2 and GTP. Here we show the effect of the increase of transglutaminase activity in Arabidopsis by using genetic transformation techniques. These lines fulfill their biological cycle normally (normal growth in soil, production of viable seeds) and show a relatively mild increase in transglutaminase activity (127%). These overexpressors of transglutaminase (OE TGase) have an extended stroma thylakoid network (71% higher number of PSIIβ centers), similar chlorophyll content (-4%), higher linear electron flow (+13%) and higher threshold of photoprotection activation (~100%). On the other hand OE TGase showed a reduced maximum photochemistry of PSII (-6.5%), a smaller antenna per photosystem II (-25%), a lower photoprotective “energization” quenching or qE (-77% at 490 μmolphotonsm-2s-1) due to a higher threshold of qE activation and slightly lower light induced proton motive force (-17%). The role of the polyamines and of the transglutaminase in the regulation of Chemiosmosis and photoprotection in chloroplasts is discussed.
-
Polyamines in Chemiosmosis in vivo: A cunning mechanism for the regulation of ATP synthesis during growth and stress
Frontiers in plant science, 2014Co-Authors: Nikolaos E. Ioannidis, Kiriakos KotzabasisAbstract:Polyamines (PAs) are low molecular weight amines that occur in every living organism. The three main PAs [putrescine (Put), spermidine (Spd) and spermine (Spm)] are involved in several important biochemical processes covered in recent reviews. As rule of thumb, increase of the cellular titer of PAs in plants is related to cell growth and cell tolerance to abiotic and biotic stress. In the present contribution, we describe recent findings from plant bioenergetics that bring to light a previously unrecognized dynamic behavior of the PA pool. Traditionally, PAs are described by many authors as organic polycations, when in fact they are bases that can be found in a charged or uncharged form. Although uncharged forms represent less than 0.1% of the total pool, we propose that their physiological role could be crucial in Chemiosmosis. This process describes the formation of a PA gradient across membranes within seconds and is difficult to be tested in vivo in plants due to the relatively small molecular weight of PAs and the speed of the process. We tested the hypothesis that PAs act as permeable buffers in intact leaves by using recent advances in vivo probing. We found that an increase of PAs increases the electric component (∆ψ) and decreases the ∆pH component of the proton motive force (pmf). These findings reveal an important modulation of the energy production process and photoprotection of the chloroplast by PAs. We explain in detail the theory behind PA pumping and ion trapping in acidic compartments (such as the lumen in chloroplasts) and how this regulatory process could improve either the photochemical efficiency of the photosynthetic apparatus and increase the synthesis of ATP or fine tune antenna regulation and make the plant more tolerant to stress.
-
Edited by:
2014Co-Authors: Kalliopi Apostolos, Kiriakos Kotzabasis, Nikolaos E. IoannidisAbstract:Polyamines in Chemiosmosis in vivo: a cunning mechanis