“…However, Mitchell's compatriot RJP Williams placed the driving force along the membrane surface and within the membrane (Williams, 1961) (Williams, 1978). Much early evidence favored the importance of Mitchell's delocalized bulk-to-bulk protonmotive force; however, by the late 1970s, substantial evidence supporting the importance of Williams's localized surface-to-surface force was beginning to accumulate (Kell, 1979) (Ferguson, 1985), and the localized protonmotive force is now widely accepted (Dilley, 2004) (Mulkidjanian et al, 2006) (Brändén et al, 2006) (Lee J. W., 2020) (Lee JW., 2020) (Springer et al, 2011) (Weichselbaum et al, 2017) (Gutman and Nachliel, 1995) (Kotlyar et al, 1994) (Heberle et al, 1994) (Nachliel and Gutman, 1996) (Gabriel and Teissie, 1996) (Gopta et al, 1999) (Cherepanov et al, 2003) (Mulkidjanian et al, 2005) (Rieger et al, 2014) (Toth et al, 2020) (Nilsson et al, 2016) (Sjöholm et al, 2017) (Morelli et al, 2020). Therefore, protons driving ATP synthesis need not come from the bulk phase, and thus the number of free protons calculated from bulk phase pH measurements may be irrelevant to bioenergetic coupling, at least under some conditions (Ferguson, 1985) (Dilley, 2004).…”