Murburn Bioenergetics and "Origins-Sustenance-Termination-Evolution of Life": Emergence of Intelligence from a Network of Molecules, Unbound Ions, Radicals and Radiations

Hyde, persona of DRS/ROS, reported in diverse contexts [97,98,99]! Slowly and surely, the murburn bioenergetics principles are being cited, discussed and accepted in scientific community [100,101,102,103,104,105,106,107,108], and some textbooks of cell biology [109] and medical biochemistry [110] have incorporated it. It is now imperative to recognize that stochastic intermolecular interactions (and electromagnetic radiations/fields thereof) and collective array of interconnected events mediated via DRS/ROS also contribute towards sustaining life, as is being explored and unraveled constantly [111]! Table 4 presents an appraisal of select systems where we have convincingly demonstrated the applicability of murburn concept.

Supposing a murburn reaction releases ~500 kJ/mol (is exergonic!), the outcome could emit: 1–2 UV/Vis photons by electronic transitions (if the states are excited), decades of IR photons by vibrational modes (perhaps the most dominant outcome!), thousands of microwave/radiowave photons (if spins or dipoles are involved, as in radical recombination and ionic current oscillations) and trillions of extremely low-frequency (ELF) quanta (if large-scale macroscopic charge mobilization occurs). The exact distribution depends on the reaction mechanism and the microenvironment (whether in water or at lipid interface). In most cases, IR dominates (explaining the higher temperature of living beings), but specialized reactions can shift into other bands, depending upon the nature of molecules involved. Table 5 presents the panoramic spectrum of interactions that the murburn paradigm could help understand, given that only murburn reactions could emanate higher energy frequency radiations. If we consider that the energy of breaking an O-O bond in a peroxide molecule is around 142–146 kJ/mol (~820 nm photon), then the explanation for photodynamic therapy (observation of increased ROS and ATP production, alteration of mitochondrial TMP, etc.) is easily afforded with the murburn theorization that the hydroxyl radical formed leads to the outcomes. Therefore, it is not anything perverse to imagine that reactions that could give high energy yields can also emit various spectral bandwidth radiations (as shown in Table 5), and all these may bring about an intermolecular or inter-structural coherence that was not deemed possible earlier. Cell biologists and medical professionals should open up their minds to these new possibilities.

Most importantly, as seen from all contemporary textbooks, the erstwhile bioenergetic explanations for cellular respiration (or photosynthesis or thermogenesis) afforded low free energy yields in their steps (examples: the highest-energy-yielding reactions of glycolysis or the Krebs cycle provide lower energy than what is afforded by ATP hydrolysis). This write-up provides a tangible connection of the stochastic ECS-DRS fulcrum of life with the impact and/or generation of radiations in (patho)physiology, of both low and high frequencies. Therefore, murburn concept constitutes a holistic perspective of matter–radiation interactions in/among living and ecological systems.

The murburn principle predates genetic mechanisms as a foundation of life; therefore, we can clearly envision how crucial it is for understanding life! In spite of having identical genes, the operation of murburn in cells induces chance-based differences between siblings; becoming a primary cause of idiosyncrasies. The classical perspectives in epigenetic and post-translational modifications are purely active-site enzyme-centered highly specific reactions. Murburn insights extend it to have relevance even outside the active site [97], independent of S-adenosyl methionine and ATP. Murburn concept can also help us reason that nucleic acid materials went on to incorporate phosphates and pentose sugar with hydroxyl groups within them to enhance the ruggedness of the molecular sequence to external radical attacks. Murburn reactions in CYP enzymes can generate genotoxic intermediates from procarcinogens. Excessive ROS (due to murburn activity in mitochondria or cytochrome P450 systems) can lead to oxidative stress, causing aberrant epigenetic changes linked to cancer initiation and progression. Increased ROS from murburn activity can mutate DNA (particularly in mitochondria!), activate oncogenes or silence tumor suppressors via epigenetic mechanisms and even affect activities of epigenetic enzymes. Cancer cells often exhibit the Warburg effect (aerobic glycolysis) and mitochondrial dysfunction, which may involve murburn-type redox processes [75]. Murburn concept provides a fresh perspective on how redox reactions influence epigenetics and cancer, particularly through ROS-mediated epigenetic alterations and metabolic rewiring.

Posing immense application potentials (refer to Table 4 for a listing of systems already unraveled) in diverse fields and offering a true possibility of understanding aging and several physiological and pathological mechanisms, DRS dynamics and murburn concept are a treasure trove waiting to be opened [115,116,117]! Further research could uncover novel biomarkers or therapies targeting murburn pathways in routine physiology/oncology and mainstream traditional Chinese/Indian ways of medicine.

Understanding any/most instantaneous molecular to macroscopic transitions (say, a photo-transduction event, or a muscle twitch or a neuron firing) would necessitate us to critically indulge several entrenched/redundant ideas/terms like proton pump, pmf & chemiosmosis [118], rotary motor-protein functions in ATP-synthesis [119] & flagellar motility [120], ETC [121] & Z-scheme [122], Kok-Joliot [123] & Quinone [124] cycles, high selectivity/flux cation pumps [125] & channels [126], etc. and have thermodynamically/kinetically justified murburn models and mechanisms in place. Paradigm inertia (reluctance of systems to change tracks), inadequate exposure or tracking of pertinent literature, established funding/publication practices, propensity for misinterpretations and aesthetic dispositions (seeing DRS as only a toxic or wasteful and unavoidable aspect of life) and the “questionable moral disposition” of some individuals are the major detriment to ushering in better health, longevity and quality of life prospects (sponsored by “murburn awareness”) for our forthcoming generations. If we have more informed and open-minded scientists, we would proceed to addressing problems such as:

Both authors contributed equally. L.J. wrote the first draft (initial murburn–coacervate–coherence parts), compiled the references and made corrections. K.M.M. added the abstract, highlights, abbreviations, summation, outstanding questions and several parts of the paper, visualized the figures, tables, boxes and communicated with the journal office, addressing the inputs and making revisions. All authors have read and agreed to the published version of the manuscript.

All data required to peruse this work are presented within the manuscript itself.

All data required to peruse this work are presented within the manuscript itself.