Evolution of the BCL-2-Regulated Apoptotic Pathway

The mitochondrion descends from a bacterium that, about two billion years ago, became endosymbiotic. This organelle represents a Pandora’s box whose opening triggers cytochrome-c release and apoptosis of cells from multicellular animals, which evolved much later, about six hundred million years ago. BCL-2 proteins, which are critical apoptosis regulators, were recruited at a certain time point in evolution to either lock or unlock this mitochondrial Pandora’s box. Hence, particularly intriguing is the issue of when and how the “BCL-2 proteins–mitochondria–apoptosis” triptych emerged. This chapter explains what it takes from an evolutionary perspective to evolve a BCL-2-regulated apoptotic pathway, by focusing on the events occurring upstream of mitochondria.