MITOCHONDRIA AND PROGRAMMED CELL-DEATH - BACK TO THE FUTURE

Programmed cell death, or apoptosis, has in the past few years undoubt edly become one of the most intensively investigated biological proces ses, However, fundamental questions concerning the molecular and bioch emical mechanisms remain to be elucidated, The central question concer ns the biochemical steps shared by the numerous death induction pathwa ys elicited by different stimuli, Heterogeneous death signals precede a common effector phase during which cells pass a threshold of 'no ret urn' and are engaged in a degradation phase where they acquire the typ ical onset of late apoptosis, Alterations in mitochondrial permeabilit y transition linked to membrane potential disruption precede nuclear a nd plasma membrane changes. In vitro induction of permeability transit ion in isolated mitochondria provokes the release of a protein factor capable of inducing nuclear chromatin condensation and fragmentation, This permeability transition is regulated by multiple endogenous effec ters, including members of the bcl-2 gene family, Inhibition of these effects prevents apoptosis.