Biochemists/biophysicists derive profound mechanistic insights from the experimental data/interpretation of probing the effects of toxic agents. Of all toxic entities known, arsenic and cyanide are the most salient ones in popular/scientific literature. Both are supposed to derail energy metabolism, with the latter being more critical. Low amounts of cyanide deleteriously impact almost instantaneously/totally at the organism level, wreaking havoc on diverse domains of cellular physiology (on powering, coherence, electro-mechanical and sensing-response activities), cutting across the living spectra of organisms. Also, the similar heme-binding triatomic anionic inhibitor of azide shows unusual enhancements and hormetic effects on redox enzyme activity. In this context, the last decade’s experimental and theoretical findings lead us to question the long-standing hemeFe-affinity ligand-binding based explanations. Conclusive evidence/arguments against the proton-centric ideas of “electron transport chain, Q-cycle, proton-pumping, proton motive force (chemiosmosis) and rotary ATP-synthesis are now available. The oxygen-centric effective charge separation (ECS) & diffusible reactive species (DRS) based murburn model affords satisfactory rationales (even for the acute/chronic toxicities presented by other diverse ions, which is discussed briefly here). The logic of authorities is also subject to the authority of logic. As the murburn theory has been around for a decade now, it is high time that the CNS (Cell, Nature and Science; also, PNAS / EMBO) of biomedical field took note! Also, the Nobel Committee must come forward to recant several of its recognitions, as the classical perceptions continue to waylay the aspirations and welfare of our younger generations. Biomed Rev 2025; 36: 1-16
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