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[Is apoptosis a "programmed cell death"?]
1Institute of Theoretical and Experimental Biophisics, Russian Academy of Science, Pushchino.
Abstract:
Many authors consider apoptosis as a programmed cell death (PCD). Their opinion is based usually on the dependence of cell death on the protein-opinion and RNA synthesis, on the intranucleosomal fragmentation of DNA and on the expression of genes, which can induce apoptosis. However our analysis of numerous literature data on the apoptotic death (judging by their morphological criteria) of different cell kinds induced by various agents shows: internucleosomal fragmentation of DNA is neither a trigger, nor a reliable proof for apoptotic death; protein- and RNA synthesis, as well as expression of P53 genes is also not a necessary condition for that and is important only in some combinations of the cell type and state and the nature of the damaging agent. Thus, the existence of immanent cell death program requires some more proofs and for present the term PCD may be undoubtedly attributed only to the genetically determined processes intended to remove such cells and organs which become unnecessary for the following development, in short, PCD is a term on the level of organism. We propose that character and sequence of destructive processes at apoptotic cell death are conditioned by the conformational changes in genome as result of the cellular environment changes caused by the action of damaging agents on the cellular membranes.
Insights
Apoptosis is not always programmed cell death (PCD). DNA fragmentation and protein synthesis are not required for apoptotic cell death, challenging the PCD definition. PCD is best defined as organism-level genetically determined removal processes.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Context:
- Apoptosis is widely considered programmed cell death (PCD), often linked to DNA fragmentation and protein synthesis.
- Existing definitions of PCD rely on specific molecular and genetic markers that may not universally apply to all apoptotic events.
Purpose:
- To critically evaluate the definition of programmed cell death (PCD) in the context of apoptosis.
- To reassess the necessity of DNA fragmentation, protein synthesis, and gene expression in apoptotic cell death.
Summary:
- Analysis of literature data suggests that internucleosomal DNA fragmentation and protein/RNA synthesis are not essential triggers or proofs of apoptotic cell death.
- The term programmed cell death (PCD) should be reserved for genetically determined developmental processes at the organism level.
- Apoptotic cell death processes are proposed to be driven by conformational genome changes resulting from altered cellular environments due to damaging agents.
Impact:
- Challenges the conventional understanding of apoptosis as universally programmed cell death (PCD).
- Suggests a re-evaluation of the criteria used to define PCD.
- Proposes a new model where environmental changes influencing cellular membranes dictate apoptotic pathways.