Template:Correction NAD and H+

Hydrogen ion ambiguities in the electron transfer system

Communicated by Gnaiger E (2023-10-08)

Electron (e^-) transfer linked to hydrogen ion (H⁺) transfer is a fundamental concept in the field of bioenergetics, critical for understanding redox-coupled energy transformations.

However, the current literature contains ambiguities regarding H⁺ formation on the negative side of bioenergetic membranes, such as the matrix side of the mitochondrial inner membrane, during oxidative phosphorylation (OXPHOS). Inconsistencies arise when examining the oxidation of NADH by respiratory Complex I or succinate by Complex II. The oxidized NAD⁺ is distinguished from NAD indicating nicotinamide adenine dinucleotide independent of oxidation state.

NADH + H⁺ → NAD⁺ +2{H⁺+e^-} is the oxidation half-reaction in this H⁺-linked electron transfer represented as 2{H⁺+e^-}. Putative H⁺ formation shown as NADH → NAD⁺ + H⁺ conflicts with chemiosmotic coupling stoichiometries between H⁺ translocation across the coupling membrane and electron transfer to oxygen. Ensuring clarity in this complex field is imperative to tackle the apparent ambiguity crisis and prevent confusion, particularly in light of the increasing number of interdisciplinary publications on bioenergetics concerning diagnostic and clinical applications of OXPHOS analysis.