Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Abstract

The basic processes harvesting chemical energy for life are driven by proton (H þ ) movements. These are accomplished by the mitochondrial redox complex V, integral membrane supramolecular aggregates, whose structure has recently been described by advanced studies. These did not identify classical aqueous pores. It was proposed that H þ transfer for oxidative phosphorylation (OXPHOS) does not occur between aqueous sources and sinks, where an energy barrier would be insurmountable. This suggests a novel hypothesis for the proton transfer. A lipid-phase-continuity H þ transfer is proposed in which H þ are always bound to phospholipid heads and cardiolipin, according to Mitchell's hypothesis of asymmetric vectorial H þ diffusion. A phase separation is proposed among the proton flow, following an intramembrane pathway, and the ATP synthesis, occurring in the aqueous phase. This view reminiscent of Grotthus mechanism would better account for the distance among the F o and F 1 moieties of F o F 1 -ATP synthase, for its mechanical coupling, as well as the necessity of a lipid membrane. A unique active role for lipids in the evolution of life can be envisaged. Interestingly, this view would also be consistent with the evidence of an OXPHOS outside mitochondria also found in non-vesicular membranes, housing the redox complexes. Journal of Cerebral Blood INTRODUCTIONChemical energy for living matter is mostly supplied by the F o F 1 -ATP synthases (ATP synthases), multimeric proteins, which employ a rotary mechanism driven by proton-motive force. In turn, protons (H þ ) are translocated by electron transport chain (ETC). The structure and organization of ATP synthases, the 'splendid nanomolecular machine' 1 that mechanically synthesize ATP from ADP and Pi are well described, but how its rotation is driven by proton flow and how this energy is converted into catalysis are less clear.2 F 1 moiety is peculiar in that it is the only enzyme as yet known channeling energy to the reactant species by means of mechanical force. The topic of H þ cycling, pivotal in oxidative phosphorylation, is central in energy conversion.

Effect of polyphenolic phytochemicals on ectopic oxidative phosphorylation in rod outer segments of bovine retina

“…Treatment of whole cells with resveratrol for some days partly restored the Fanconi anaemia mitochondrial metabolic activity while decreasing oxygen uptake in wild‐type cells (Columbaro et al ., ). The effects of N,N_‐dicyclohexylcarbodiimide and oligomycin are different as they act on the F o moiety in the lipid phase (Morelli et al ., ).…”

Extramitochondrial energy production in platelets

“…The fact that platelets do not contain a double‐membrane system similar to that of mitochondria, where to accumulate protons, may seem to represent a conceptual difficulty in the hypothesis about an ectopic OXPHOS metabolism conduction. However, an H + delivery at the centre of a membrane expressing the electron transfer chains [Morelli et al., ], which has found many experimental confirms [Cherepanov et al., ; Mulkidjanian, ], would apply also to platelets. Notably, it was reported that, in a mitochondrion, the free protons are too few to sustain the ATP synthase activity [Bal et al., ] and that the ΔpH across the inner mitochondrial membrane is low [Żurawik et al., ] and opposite with respect to that supposed by the chemiosmotic theory [Tupper and Tedeschi, ].…”

Metabolic Alterations in Inherited Cardiomyopathies

“…Besides the structural function, CL is required for the enzymatic activity of complex II, where one CL molecule is located near the binding site for ubiquinone, suggesting that CL is involved in the proton pumping mechanism. A role for CL in proton transport has been recently proposed also for complex IV [171]. In cellular models of BTHS, including patient-derived iPSC, oxygen consumption at the respiratory chain is reduced, reflecting the impaired activity of individual respiratory chain complexes and diminished energetic coupling between complexes [148,154,156].…”