If intact isolated mitochondria are provided with NADH (or a source of FADH₂ such as succinate) plus O₂ and P_i, but not ADP, the oxidation of NADH and the reduction of O₂ rapidly cease as the amount of endogenous ADP is depleted by ATP formation. If ADP is then added, the oxidation of NADH is rapidly restored. Thus mitochondria can oxidize FADH₂ and NADH only as long as there is a source of ADP and P_i to generate ATP. This phenomenon, termed respiratory control, occurs because oxidation of NADH and succinate (FADH₂) is obligatorily coupled to proton transport across the inner mitochondrial membrane. If the resulting proton-motive force is not dissipated during the synthesis of ATP from ADP and P_i (or during other energy-requiring processes), both the transmembrane proton concentration gradient and the membrane electric potential will increase to very high levels. At this point, pumping of additional protons across the inner membrane requires so much energy that it eventually ceases, blocking the coupled oxidation of NADH and other substrates.