Why Two Pathways in C. elegans?
Why does C. elegans need two pathways when mammals need only the indirect pathway to efficiently induce apoptosis? One possibility is that two pathways are put to work in C. elegans in order to ‘speed things up’. In contrast to cultured mammalian cells, in which the apoptotic process can take hours if not days, apoptosis is a very rapid process in C. elegans: it takes only about 20 min from the first sign of apoptosis until the doomed cell is engulfed by a neighboring cell. We favor the hypothesis that worms and mammals might not be that different and that both pathways, the direct and indirect pathway, might be at work in mammals as well. The idea that a direct pathway also functions in mammals fell out of favor mainly because of the lack of evidence for a physical interaction between antiapoptotic Bcl-2 proteins and Apaf-1.25 However, the recent analysis of mice expressing a mutant cytochrome c protein unable to bind to Apaf-1 (and hence, most likely unable to activate the apoptosome
