Apoptotic cell death can occur by two different pathways. Type 1 is initiated by the activation of death receptors (Fas, TNF-receptor-family) on the plasma membrane followed by activation of caspase 8. Type 2 involves changes in mitochondrial integrity initiated by various effectors like Ca(2+), reactive oxygen species (ROS), Bax, or ceramide, leading to the release of cytochrome c and activation of caspase 9. The release of cytochrome c is followed by a decrease of the mitochondrial membrane potential DeltaPsi(m). Recent publications have demonstrated, however, that induction of apoptosis by various effectors involves primarily a transient increase of DeltaPsi(m) for unknown reason. Here we propose a new mechanism for the increased DeltaPsi(m) based on experiments on the allosteric ATP-inhibition of cytochrome c oxidase at high matrix ATP/ADP ratios, which was concluded to maintain low levels of DeltaPsi(m) in vivo under relaxed conditions. This regulatory mechanism is based on the potential-dependency of the ATP synthase, which has maximal activity at DeltaPsi(m)=100-120 mV. The mechanism is turned off either through calcium-activated dephosphorylation of cytochrome c oxidase or by 3,5-diiodo-L-thyronine, palmitate, and probably other so far unknown effectors. Consequently, energy metabolism changes to an excited state. We propose that this change causes an increase in DeltaPsi(m), a condition for the formation of ROS and induction of apoptosis.