Oxidative phosphorylation revisited

Sunil Nath, John Villadsen

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The fundamentals of oxidative phosphorylation and photophosphorylation are revisited. New experimental data on the involvement of succinate and malate anions respectively in oxidative phosphorylation and photophosphorylation are presented. These new data offer a novel molecular mechanistic explanation for the energy coupling and ATP synthesis carried out in mitochondria and chloroplast thylakoids. The mechanism does not suffer from the flaws in Mitchell's chemiosmotic theory that have been pointed out in many studies since its first appearance 50 years ago, when it was hailed as a ground‐breaking mechanistic explanation of what is perhaps the most important process in cellular energetics. The new findings fit very well with the predictions of Nath's torsional mechanism of energy transduction and ATP synthesis. It is argued that this mechanism, based on at least 15 years of experimental and theoretical work by Sunil Nath, constitutes a fundamentally different theory of the energy conversion process that eliminates all the inconsistencies in Mitchell's chemiosmotic theory pointed out by other authors. It is concluded that the energy‐transducing complexes in oxidative phosphorylation and photosynthesis are proton‐dicarboxylic acid anion cotransporters and not simply electrogenic proton translocators. These results necessitate revision of previous theories of biological energy transduction, coupling, and ATP synthesis. The novel molecular mechanism is extended to cover ATP synthesis in prokaryotes, in particular to alkaliphilic and haloalkaliphilic bacteria, essentially making it a complete theory addressing mechanistic, kinetic, and thermodynamic details. Finally, based on the new interpretation of oxidative phosphorylation, quantitative values for the P/O ratio, the amount of ATP generated per redox package of the reduced substrates, are calculated and compared with experimental values for fermentation on different substrates. It is our hope that the presentation of oxidative phosphorylation and photophosphorylation from a wholly new perspective will rekindle scientific discussion of a key process in bioenergetics and catalyze new avenues of research in a truly interdisciplinary field.
Original languageEnglish
JournalBiotechnology and Bioengineering
Issue number3
Pages (from-to)429-437
Publication statusPublished - 2015


  • Bioenergetics
  • Molecular mechanism
  • Oxidative phosphorylation
  • Photosynthesis
  • F1FO‐ATP synthase
  • Mitchell's chemiosmotic theory
  • Nath's torsional mechanism of energy transduction and ATP synthesis
  • Ion and energy coupling
  • Anions
  • Succinate
  • Malate
  • Cotransporter
  • P/O ratio
  • Uncoupler
  • Unified theory of ATP synthesis and hydrolysis
  • Alkaliphilic bacteria


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