Apoptosis in Living Animals Is Assisted by Scavenger Cells and Thus May Not Mainly Go through the Cytochrome C-Caspase Pathway.

Because billions of cells die every day in their bodies, animals have evolutionarily developed apoptosis to preserve the tissue environment from adverse effects of dead cells, a process achieved via phagocytosis of the cell corpses by professional or amateur phagocytes that are collectively referred to as scavengers. Hence, apoptosis is a merger of two procedures separately occurring inside the dying and the scavenger cells, respectively. The task of apoptosis research is to study how these death procedures occur without hurting the host tissues, and recruitment of in vitro system into the study must be justified for this purpose. Cells in culture have no motivation to preserve the environment, and their death does not involve corpse clearance by scavengers. Therefore, programmed cell death in culture should be redefined, for example as stress-induced cell death, to avoid many sources of confusions, since the word "apoptosis" had already been defined, prior to the era of cell culture, as a silent and beneficial cell suicide with corpse clearance as a distinctive hallmark. We should start over again on apoptosis research by determining whether different physiological apoptotic procedures in animals involve the cytochrome c-caspase pathway, since it has been established from cultured cells as a central mechanism of "apoptosis" but whether it overarches any physiological apoptotic procedure in animals is still unclear. Probably, cells in living animals are programmed to use scavengers to assist their apoptosis but cells in culture have no scavengers to help and thus need to go mainly through the cytochrome c-caspase pathway.