In a recent publication, Manoj raises criticisms against consensus views on the ATP synthase. The radical statements and assertions are shown to contradict a vast body of available knowledge that includes i) pioneering single-molecule biochemical and biophysical studies from the respected experimental groups of Kinosita, Yoshida, Noji, Börsch, Dunn, Gräber, Frasch, and Dimroth etc., ii) state-of-the-art X-ray and EM/cryo-EM structural information garnered over the decades by the expert groups of Leslie-Walker, Kühlbrandt, Mueller, Meier, Rubinstein, Sazanov, Duncan, and Pedersen on ATP synthase, iii) the pioneering energy-based computer simulations of Warshel, and iv) the novel theoretical and experimental works of Nath. Valid objections against Mitchell's chemiosmotic theory and Boyer's binding change mechanism put forth by Manoj have been addressed satisfactorily by Nath's torsional mechanism of ATP synthesis and two-ion theory of energy coupling and published 10 to 20 years ago, but these papers are not cited by him. This communication shows conclusively and in great detail that none of his objections apply to Nath's mechanism/theory. Nath's theory is further consolidated based on its previous predictive record, its consistency with biochemical evidence, its unified nature, its application to other related energy transductions and to disease, and finally its ability to guide the design of new experiments. Some constructive suggestions for high-resolution structural experiments that have the power to delve into the heart of the matter and throw unprecedented light on the nature of coupled ion translocation in the membrane-bound FO portion of F1FO-ATP synthase are made.
Keywords: Bioenergetics; Boyer's binding change mechanism of ATP synthesis; Diffusible reactive oxygen species (DROS); Mitchell's chemiosmotic theory; Molecular mechanism, thermodynamics, kinetics, and transport in ATP synthase; Nath's torsional mechanism of energy transduction and ATP synthesis; Nath's two-ion theory of energy coupling in ATP synthesis; Oxidative phosphorylation (OXPHOS); Photophosphorylation (PHOTOPHOS); Photosynthesis.
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