Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation

Cobra Venom Cytotoxins as a Tool for Probing Mechanisms of Mitochondrial Energetics and Understanding Mitochondrial Membrane Structure

“…Noteworthily, additional biochemical studies of ATP synthases reconstituted in liposomes also yielded results supporting the concept of a bi-facing orientation of the F1 subunits, in agreement with the localized coupling of protons [116]. Remarkably, localized coupling is also supported by a recently introduced novel concept that links extra-mitochondrial OxPhos in the ER to glucose metabolism coupled to the pentose phosphate pathway in a closed-loop process [99]. In our view, the experimental evidence presented in this review does support localized proton coupling with the protons moving according to the Grotthuss mechanism via the polar heads of phospholipids on the membrane surface.…”

“…These observations assume that mitochondria transfer the OxPhos machinery to the ER, rendering the ER's ability for aerobic ATP synthesis [91,95,97]. In fact, it has recently been demonstrated that mitochondria generate the necessary vesicles that provide the ER with the necessary OxPhos components [98,99]. However, this phenomenon is not ubiquitous and is restricted to a small number of specialized cell types, as supported by the findings in recent years describing extra-mitochondrial OxPhos in cellular districts including rod outer segment discs [100][101][102][103], platelets [104], cell plasma membrane [105][106][107][108][109], exosomes, and microvesicles [110,111].…”