Secondary necrosis: the natural outcome of the complete apoptotic program

The predominant definition of apoptosis considers that the elimination of the apoptosing cell is by heterolytic degradation following phagocytosis by an assisting scavenger (efferocytosis). However, an alternative and largely underestimated outcome of apoptosis is secondary necrosis, an autolytic process of cell disintegration with release of cell components that occurs when there is no intervention of scavengers and the full apoptotic program is completed. Secondary necrosis is the typical outcome of apoptosis in unicellular eukaryotes but, importantly, it may also occur in multicellular animals and has been implicated in the genesis of important human pathologies. Secondary necrosis is a mode of cell elimination with specific molecular and morphological features and should be considered the natural outcome of the complete apoptotic program.