Chemiosmotic and murburn explanations for aerobic respiration: Predictive capabilities, structure-function correlations and chemico-physical logic
Authors: Nikolai Mikhailovich Bazhin
Abhinav Parashar
Kannan Pakshirajan
Manish Kumar
Daniel Andrew Gideon
Afsal Manekkathodi
Vidhu Soman
Surjith Ramasamy
Kelath Murali Manoj
Vivian David Jacob
Journal: Archives of Biochemistry and Biophysics (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Aerobic respiration; Bioenergetics; Chemiosmosis; Kinetics; Mitochondrial complexes
Affiliations: Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala, 679122, India. Electronic address: ., Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, 110016, India., Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala, 679122, India., Department of Biotechnology, Vignan's Foundation for Science, Technology & Research, Vadlamudi, Guntur, 522213, India., Department of Biotechnology & Bioinformatics, Bishop Heber College (Autonomous), Tennur, Tiruchirappalli, 620017, India., Qatar Environment and Energy Research Institute, Hamad Bin Khalifa University, Al-Rayyan PO Box 34110, Qatar., Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India., Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, St. Institutskaya 3, 630090, Novosibirsk, Russia. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 This paper intends to show that the oxidative phosphorylation occurs through a mechanism based on diffusible oxygen radicals. It contains too many errors to dissect, and I show below only a few of them: ![file] ![file] ![file] Authors also use erroneous citations in support of their claims: e.g. they claim that  The anoxic ET between the two heme a of Comp. IV afforded several orders lower rates when compared to the overall ETC rates and offer as support the publication  Early molecular events in the reaction of fully reduced cytochrome oxidase with oxygen at room temperature ( In Biophysical Chemistry of Dioxygen Reactions in Respiration and Photosynthesis: Proceedings of the Nobel Conference Held at Fiskebu00e4ckskil, Sweden, 1-4 July 1987 (Chimca Scripta, 28, pp. 63-69) . This reference, however, does not deal with anoxic electron-transfer, but with conformational changes ellicited by the binding of O2 to complex IV prior to electron-transfer. Authhors also state  In the chemiosmotic proposal, it is assumed that the work expended [in transporting protons from the matrix to the intermembrane space] is converted into the potential energy of this system with the concomitant generation of a concentration gradient. However, this view is inconsistent with the known concepts of thermodynamics wherein it is a fundamental principle that ideal solutions of different concentrations do not have potential energy and there is no heat release with simple irreversible mixing [81]. Therefore, it follows that the work expended on creating any concentration gradient must be dissipated in the form of heat in the environment. As a result, protons passing or returning through Complex V cannot perform the work of the endergonic ATP-synthesis. This confusing paragraph completely neglects the well-known fact that Gibbs free energy is a state function and does not depend on the path taken to achieve a state. The Gibbs free energy of a neutral molecule in a compartment with a given concentration will necessarily be higher that the free energy of that same molecule at a compartment with a lower concentration, and therefore there IS, indeed, a potential energy difference stored in the concentration gradient. For a charge species, one must also take intoo account the electric potential in each compartment, but hte same principle applies: if the electrochemical potential of a proton in the inter-membrane space is higher that the electrochemical potential of the proton in the matrix (whether due to a lower concentration in the matrix, a lower potential in the matrix, or a mixture of both effects). the movement of the proton towards the matrix will necessarily by spontaneous and it can be coupled to another chemical reaction to help dirve it to completion. All of this is standard knowledge and authors should not pretend that any special mystery exists.... , 
 Bogus identity, humbug! , 
 When people pull down someone s works anonymously, and when they moderate and screen out comments and do not consider the malicious nature of such ventures, there is no point in sparring over such platforms. , 
 It is really sad to see that people do not come forward to accept their identitity and opinion in scientific discussions. For those that really care for the subject and don t believe in taking potshots and negativity, I urge them to read: Manoj KM, Ramasamy S, Parashar A, Gideon DA, Soman V, Jacob VD, and Pakshirajan K. (2020a). Acute toxicity of cyanide in aerobic respiration: Theoretical and experimental support for murburn explanation. Biomolecular Concepts (De Gruyter) 11, 32-56. doi: 10.1515 bmc-2020-0004 (Published on 17th March, 2020) Manoj KM* Bazhin NM (2021) Progress in Biophysics and Molecular Biology. The murburn precepts of aerobic respiration and redox homeostasis. doi: 10.1016 j.pbiomolbio.2021.05.010 Gideon DA, et al. Manoj KM* (2021) Journal of Biomolecular Structure and Dynamics. Mechanism of electron transfers mediated by cytochromes c and b5 in mitochondria and endoplasmic reticulum: Classical and murburn perspectives. doi: 10.1080 07391102.2021.1925154 Manoj KM* (2020) Biomedical Reviews 31, 135. In defense of the murburn explanation for aerobic respiration. (Includes a Supplementary Information file that points out the lack of consensus in the field and also shows how entrenched critical peers lack basic sense of integrity while pulling down others meticulous works.) http: dx.doi.org 10.14748 bmr.v31.7713 http: dx.doi.org 10.14748 bmr.v31.7714 , 
 Last time I tried to post a comment after logging in as the author, it asked me to verify my identity repeatedly and did not send the verification email either to my account. I guess this website is just a tool of some powerful people in the establishment. All that these detracting peers have to do to bring my group s work down legitimately is write to the journal office where the papers were published and offer the editor their rebuttals to what we have found and advocated. Since our pursuits are anti-establishment, they can easily get their works published. But then, with that exercise, they will have to reveal their identity. That will not allow them to make a volte face when our theory prevails. Yet, I respect Pedro Silva s approach for coming out in the open to defend chemiosmosis, but he has not done any justice to the volume of arguments evidence we presented against the classical bioenergetics paradigm. Further, he has not addressed the volume of works that supports the murburn theory either. And he shall go down in history as a vain martyr, sacrificed by the puppeteers that seem to shepherd goad such pursuits. Pubpeer can go ahead and allow anonymous people to malign my works. But your progeny will study and benefit out of the critical insights my group s works have offered. This is sad! There is no accountability or transparency in your system. People write comments like they understand the work and pose to be experts, all the while ovelooking and slanting meticulous works and systematically waylaying somebody s legitimate progression. One goes through dozens of journals to have a counter-current paper published. Then there is this platform where every Tom, Dick and Harry get to pull down such works..... I shall not defend my works anymore on this portal, as this is a vain exercise that just wastes my time and unnecessarily gives the vanities here some credibility. ,