The scientists conducted their research using the transparent nematode worm, Caenorhabditis elegans, long employed as a model to study apoptosis. The tiny worm contains exactly 1,090 cells, of which 131 undergo apoptosis, most during embryonic development. Genetic studies of mutant worms that lacked one or another of these proteins had shown that they affected one another. Thus, said Hersh, he and his colleagues used antibodies that tagged each protein involved in apoptosis to reveal their cellular locations. Their experiments involved eliminating one or another of the signal proteins and studying the effects on protein localization.
Mitochondria are the energy-producing powerhouses of the cell.
After all, the mammalian counterpart of CED-4 is found mainly in the cytoplasm, and there was no indication that it would go to the membrane surrounding the nucleus. Still mysterious, say Horvitz and Hersh, is how CED-4 reaches the nuclear membrane. They are studying CED-4 mutants that fail to reach the nucleus. Such mutants might reveal clues to the transport process and its importance in cell death. While the discovery of CED-4's translocation to the nuclear membrane is a basic one, it could have eventual clinical implications, said Hersh.