The evolution of a mechanism of cell suicide

Abstract

In the vertebrates, programmed cell death or apoptosis frequentlyinvolves the relocalization of mitochondrial cytochrome c to thecytoplasm. This prominent role in the regulation of apoptosis is inaddition to the primary function of cytochrome c in the mitochondrialelectron transport chain. These seemingly divergent roles becomeplausible when considering the symbiotic origin of the mitochondrion.Symbiosis involves conflicts between levels of selection, in this casebetween the primitive host cell and the protomitochondria. in an aerobicenvironment, selection on the protomitochondria may have favored routinemanipulations of the host cell's phenotype using products andby-products of oxidative phosphorylation, in particular reactive oxygenspecies (ROS). Blocking the mitochondrial electron transport chain byremoving cytochrome c enhances the production of ROS; thus cytochrome crelease by protomitochondria may have altered the host cell's phenotypevia enhanced ROS production. Subsequently, this signaling pathway mayhave been refined by selection so that cytochrome c itself became thetrigger for changes in the host's phenotype. A mechanism of apoptosis inmetazoans may thus be a vestige of evolutionary conflicts within theeukaryotic cell. (C) 1999 John Wiley a Sons, Inc.