A new model for mitochondrial membrane potential production and storage

Mitochondrial membrane potential (MMP) is the most reliable indicator of mitochondrial function. The MMP value range of −136 to −140 mV has been considered optimal for maximum ATP production for all living organisms. Even small changes from the above range result in a large fall in ATP production and a large increase in ROS production. The resulting bioenergetic deregulation is considered as the causative agent for numerous major human diseases. Normalization of MMP value improves mitochondrial function and gives excellent therapeutic results. In order for a systematic effective treatment of these diseases to be developed, a detailed knowledge of the mechanism of MMP production is absolutely necessary. However, despite the long-standing research efforts, a concrete mechanism for MMP production has not been found yet.The present paper proposes a novel mechanism of MMP production based on new considerations underlying the function of the two basic players of MMP production, the electron transport chain (ETC) and the F1F0 ATP synthase. Under normal conditions, MMP is almost exclusively produced by the electron flow through ETC complexes I–IV, creating a direct electric current that stops in subunit II of complex IV and gradually charges MMP. However, upon ETC dysfunction F1F0 ATP synthase reverses its action and starts to hydrolyze ATP. ATP hydrolysis further produces electric energy which is transferred, in the form of a direct electric current, from F1 to F0 where is used to charge MMP. This new model is expected to redirect current experimental research on mitochondrial bioenergetics and indicate new therapeutic schemes for mitochondrial disorders.