The evolution of a mechanism of cell suicide

In the vertebrates, programmed cell death or apoptosis frequently involves the relocalization of mitochondrial cytochrome c to the cytoplasm. This pro minent role in the regulation of apoptosis is in addition to the primary fu nction of cytochrome c in the mitochondrial electron transport chain. These seemingly divergent roles become plausible when considering the symbiotic origin of the mitochondrion. Symbiosis involves conflicts between levels of selection, in this case between the primitive host cell and the protomitoc hondria. in an aerobic environment, selection on the protomitochondria may have favored routine manipulations of the host cell's phenotype using produ cts and by-products of oxidative phosphorylation, in particular reactive ox ygen species (ROS). Blocking the mitochondrial electron transport chain by removing cytochrome c enhances the production of ROS; thus cytochrome c rel ease by protomitochondria may have altered the host cell's phenotype via en hanced ROS production. Subsequently, this signaling pathway may have been r efined by selection so that cytochrome c itself became the trigger for chan ges in the host's phenotype. A mechanism of apoptosis in metazoans may thus be a vestige of evolutionary conflicts within the eukaryotic cell. (C) 199 9 John Wiley a Sons, Inc.