Interaction of membrane-embedded cytochrome b-complexes with quinols: Classical Q-cycle and murburn model

We recently proposed a diffusible reactive (oxygen) species (DRS/DROS) based function for cytochrome b complexes (CBC) and quinones (Q)/quinols (QH₂ ) in the murburn model of bioenergetics. This proposal is in direct conflict with the classical purview of Q-cycle. Via extensive analyses of the structure-function correlations of membrane-quinones/quinols and proteins, we present qualitative and quantitative arguments to infer that the classical model cannot explain the energetics, kinetics, mechanism and probabilistic considerations. Therefore, it is proposed that Q-cycle is neither necessary nor feasible at CBCs. In contrast, we substantiate that the murburn model explains: (a) crucial structural data of CBCs, (b) why quinones/quinols are utilized in bioenergetic membranes, (c) how trans-membrane potential is generated owing to effective charge separation at CBCs, (d) mobility data of O₂ , DRS, Q/QH₂ , and (e) utility of other reaction/membrane components. Further, the murburn model also accommodates the absence of quinones in anaerobic Archaea, wherein methanophenazines are prevalent. The work mandates that the textbooks and research agendas are refreshed to reflect the new perception. SIGNIFICANCE: The current article must be seen as a critical and detailed analysis of the role and working mechanism of quinone (Q) /quinols (QH₂ ) in bioenergetic membranes. In the classical model, QH₂ are perceived as highly mobile electron-transport agents that bind and donate electrons to cytochrome b complexes (CBCs), using sophisticated electronic circuitries, in order to recycle Q and pump protons. The classical perception sees radicals (such as Q*-, O₂ *-, etc., also called diffusible reactive species, DRS) as wasteful or toxic (patho) physiological manifestations. It is highlighted herein that QH₂ has low mobility and matrix has little protons to pump. New insights from the structural analyses of diverse CBCs and quinols, in conjunction with murburn reaction thermodynamics suggest that the electrons from substrates/quinols are effectively utilized via DRS. This perception fits into a much broader analysis of 1 and 2 electron transfers in overall redox metabolism, as recently brought out by the murburn model, wherein DRS are considered obligatory ingredients of physiology. Thus, the findings mandate a reorientation in the pertinent research field.