Redundant cell death mechanisms as relics and backups

Abstract

Here we review recent observations indicating the existence of redundant cell death mechanisms. We speculate that this redundancy reflects a particular evolutionary history for cellular demise. Autophagic or apoptotic elements might have been added to a primordial death mechanism, initially improving cell dismantling and later acquiring the ability to act themselves as death effectors. The resulting redundancy of cell death mechanisms has pathophysiological implications.

Bcl-2 family members: Dual regulators of apoptosis and autophagy

“…Such catabolic reactions would have been "invented" by evolution first at the unicellular level-and hence affect portions of the cell rather than the entire cell-and later would have been used in metazoans for the elimination of entire cells by apoptosis. 52 Another major implication of the overlapping regulation of autophagy and apoptosis relates to the role of pro-apoptotic Bcl-2 proteins as tumor suppressors and that of anti-apoptotic proteins as oncogenes. The oncogenic potential of Bcl-2 family members has been attributed to disabled apoptosis, 24 which is one of the hallmarks of cancer.…”

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

“…23 In some instances, caspase inhibition simply induces a shift from an apoptotic morphology to a mixed morphology or even to full-blown pictures of necrotic or autophagic cell death, which, however, can manifest with some delay. 24 So under certain circumstances, an alternative to 'caspase-dependent death' may be 'Z-VAD-fmk-inhibitable chromatin condensation', if there is no information on the longterm behavior of the experimental system. 'Caspase independent cell death' (CICD) 23 can occur despite the effective inhibition of caspases and can manifest with the morphological signs of apoptosis, autophagy or necrosis.…”

Tumor stress, cell death and the ensuing immune response

“…12 Apoptosis is a rapid form of cell death, characterized by the rounding of the cell, retraction of pseudopodes, chromatin condensation (pyknosis), nuclear fragmentation (karrhyorhexis), and plasma membrane blebbing. 13 In contrast, necrotic cell death is characterized by the swelling of cytoplasm (oncosis) and cytoplasmic organelles leading to the disruption of the plasma membrane. Necrosis is commonly considered as a pathological process that is often associated with local inflammation eventually supporting tumor development.…”