A classical lay summary by Satish Raut, from the The Ohio State University.
Prof. Peter D. Mitchell proposed the proposed the chemiosmosis mechanism in 1961. He hypothesized that ‘ATP synthesis in respiring cells comes from the electrochemical gradient across the inner mitochondrial membrane by using NADH and FADH2; formed during the oxidative breakdown of glucose’1. This work was highly criticised by Tager, Veldsema-Currie and Slater. They stated that the apparent failure of the mitochondria to oxidize NADH under the conditions of their experiments is due to loss of various components during the preincubation period2.
They were not able to recapitulate the chemiosmotic hypothesis of Peter D. Mitchell. In response to that Peter D. Mitchell and J Moyle gave the proof of concept in their paper, that they did not observe any dysfunctionality during the experiment even for anaerobic incubation times as long as 60 min3. Further, they concluded that it is difficult to copy experimental techniques in every detail3. In addition, P Mitchell and J Moyle pointed out that Slater et al. might failed to recapitulate due to insufficient attention to certain technical points. For example, mitochondrial damage may result from insufficiently strict anaerobiosis during preincubation; and such damage might have impaired NADH oxidation in their experiments3.
On the other hand, it seems distinctly possible that NADH oxidation did occur in the experiments of Slater et al. but they have so far failed to measure it3. Finally, they concluded that the result described in this paper provide the strong evidence that their earlier interpretation of chemiosmosis using oxygen pulses of some 1 µg atom oxygen/g mitochondrial protein, two of the six proton equivalents translocated during β-hydroxybutyrate oxidation by rat liver mitochondria are accounted for by a rotenone sensitive region Site 1 of the respiratory chain, associated with NADH oxidation, which is not utilized in the oxidation of succinate3. Finally, the mechanism of chemiosmosis was widely accepted and Prof. Peter. D. Mitchell got the Nobel prize.
References
1. MITCHELL, P. Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism. Nature 191, 144–148 (1961). https://doi.org/10.1038/191144a0
2. TAGER, J., VELDSEMA-CURRIE, R. & SLATER, E. Chemi-Osmotic Theory of Oxidative Phosphorylation. Nature 212, 376–379 (1966). https://doi.org/10.1038/212376a0
3. MITCHELL, P., MOYLE, J. Chemiosmotic Hypothesis of Oxidative Phosphorylation. Nature 213, 137–139 (1967). https://doi.org/10.1038/213137a0