Mitochondrial outer membrane permeabilization (MOMP) determines the point-of-no-return of most if not all signal-transduction cascades leading to cell death. It has been postulated that the molecular mechanism leading to MOMP could depend on the activation of the mitochondrial fission machinery mediated by proteins from the dynamin superfamily. However, recent work suggests that, depending on the specific apoptosis induction pathway, mitochondrial fission can occur independently or downstream from MOMP. Moreover, fragmentation of the mitochondrial network can inhibit MOMP and apoptosis in response to a particular range of lethal stimuli, namely those relying on Ca(2+) waves. Failure to transmit the Ca(2+) wave through disconnected mitochondria then interrupts the propagation of the pro-apoptotic signal. Thus, mitochondrial fission can either enhance or reduce the probability of MOMP and consequent cell death, depending on the initial lethal stimulus.