Extra-mitochondrial ATP synthesis, proton dynamics at the membrane, and mitochondria-derived vesicles: Current findings and considerations

Adenosine triphosphate (ATP) is essential for almost all life forms. In our article, we discuss (i) insights into the bioenergetics of ATP generation, including an extended view of proton currents during oxidative phosphorylation (OXPHOS), (ii) experimental work showing the ability of several biological structures to perform extra-mitochondrial OXPHOS, (iii) the role of mitochondria-derived vesicles (MDVs) in extra-mitochondrial OXPHOS, and (iv) the relevance of these aspects for the interpretation of the human brain map of mitochondrial density and ATP-synthesizing capacity. In our opinion, extra-mitochondrial OXPHOS and MDVs are important topics for future research that will significantly expand our picture of cellular bioenergetics. • Interfacial and intramembrane proton channels are important for ATP synthesis • Mitochondria-derived vesicles can synthesize ATP • Extra-mitochondrial OXPHOS needs to be considered when interpreting brain mitochondrial data