Problematic issues of ATP synthesis in vivo

The work is devoted to description of processes that provide fundamental conditions for ATP synthesis in vivo. The work presents information on the basis of which a general fundamental picture of formation of electrochemical gradient on the mitochondrial (or chloroplast) membrane and its use for ATP-synthase operation is described. An attempt was made to explain the order of appearance of electrical and chemical gradients, as well as the feedback between electrical and chemical components of the driving force in mitochondria and chloroplasts based on Nath's two-ion theory. The results of the analysis allowed us to conclude that a series of sequential events (which are separated in time and space) is necessary for ATP synthesis in vivo, namely: formation of electrical potential, formation of chemical potential, their use for ATP synthase operation. The electrical component is formed due to light energy (chloroplast) or metabolite-associated processes (mitochondria) by pumping of H⁺ by the electron transport chain. Formation of chemical gradients occur only upon collapse of the electrical gradient by counterion translocation. As a result of their interaction, a driving force (plus change in the conformation of membrane components) is formed on the membrane, which makes ATP-synthase work. The reasons for significant differences in the values of the chemical and electrical components of the gradient on the membranes of mitochondria and chloroplasts are shown (explained). Analysis of the active transport of metabolites from the mitochondria allows us to conclude that it is possible to “break” the concentration flow of Krebs cycle metabolites into mitochondria in vivo, which can be maintained by cytoplasmic malate.