Apoptosis: A Programme of Cell Death or Cell Disposal?

Based primarily on morphological features, apoptosis was described as the cell death that occurs during physiological situations, whereas necrosis was observed during acute harmful conditions. Apoptosis was, therefore, associated with a programme of cell death, as opposed to necrosis, considered an accidental, uncontrolled, pathological cell death. The apoptotic machinery was first unravelled in the nematode Caenorhabditis elegans, where a protease called CED‐3 was central to the execution of cells destined to die. Inactivation of ced‐3 gene prevents developmental cell death in the worm, an observation that reinforces the notion that apoptosis holds the switch between life and death. In mammals, proteins homologous to CED‐3, members of the family collectively called caspases, are considered the executioner proteases responsible for generating fundamentally all aspects of apoptosis. However, inhibition of the so‐called executioner caspases (i.e. inhibition of apoptosis) does not prevent cell death to occur. Consequently, in mammals, the decision switch between life and death resides upstream of the activation of caspases and the ensuing apoptotic cell death. Therefore, apoptosis is not a programme of cell death but purely a termination step of a cell death programme, responsible for proper disposal of the already‐committed, dying cells.