It was recently shown that, in progressively depolarizing mitochondria, the F0-F1 ATP synthase and the adenine nucleotide translocase (ANT) may change directionality independently from each other (Chinopoulos et al.  FASEB J. 24:2405). When the membrane potentials at which these two molecular entities reverse directionality, termed reversal potential (Erev), are plotted as a function of matrix ATP/ADP ratio, an area of the plot is bracketed by the Erev_ATPase and the Erev_ANT, which we call “B space”. Both reversal potentials are dynamic, in that they depend on the fluctuating values of the participating reactants; however, Erev_ATPase is almost always more negative than Erev_ANT. Here we review the conditions that define the boundaries of the “B space”. Emphasis is placed on the role of matrix substrate-level phosphorylation, because during metabolic compromise this mechanism could maintain mitochondrial membrane potential and prevent the influx of cytosolic ATP destined for hydrolysis by the reversed F0-F1 ATP synthase. © 2011 Wiley-Liss, Inc.