The Mitochondrion as a Sensor/Effector of Oxidative Stress During Apoptosis

The process of apoptosis can be subdivided into at least three different phases. During the initiation phase cells either suffer subnecrotic damage or receive "death signals" via specific receptors (or are deprived of "survival signals") (1-5). Nonspecific or receptormediated death induction involves a stimulus-dependent ("private") biochemical pathway, and it is only after this initiation phase that common pathways come into action. It is generally assumed that the execution phase of apoptosis defines the "decision to die" at the "point of no return" of the apoptotic cascade. It is at this level that the different private pathways converge into one (or few) common pathway(s) and that cellular processes (redox potentials, expression levels of oncogene products, etc.) still have a decisive regulatory function. Once the cell has been irreversibly committed to death, the different manifestations classically associated with apoptosis such as DNA fragmentation become manifest. This degradation phase is the same in all cell types and involves the action of catabolic enzymes including nucleases and proteases.