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On the origin, evolution, and nature of programmed cell death: a timeline of four billion years
1EMI-U 9922 INSERM/Université Paris 7, IFR 02, Hôpital Bichat-Claude Bernard, AP-HP, 46 rue Henri Huchard, 75877 Paris cedex 18, France. ants@club-internet.fr
Abstract:
Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new level of complexity, with important therapeutic implications, has begun to emerge, suggesting (i) that several different self-destruction pathways may exist and operate in parallel in our cells, and (ii) that molecular effectors of cell suicide may also perform other functions unrelated to cell death induction and crucial to cell survival. In this review, I will argue that this new level of complexity, implying that there may be no such thing as a 'bona fide' genetic death program in our cells, might be better understood when considered in an evolutionary context. And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms.
Insights
Programmed cell death, a key process in multicellular life, is complex. Understanding its evolutionary origins in single-celled organisms offers new therapeutic insights.
Area of Science:
- Cellular Biology
- Evolutionary Biology
- Molecular Biology
Background:
- Programmed cell death is a genetically regulated process vital for multicellular organism development and homeostasis.
- Dysregulation of cell suicide mechanisms contributes to various diseases.
- Recent findings reveal complexity in cell death pathways, with effectors having roles beyond cell death.
Purpose of the Study:
- To explore the complexity of programmed cell death pathways.
- To argue for an evolutionary perspective in understanding cell suicide mechanisms.
- To investigate the origins of regulated cell suicide in ancestral single-celled organisms.
Main Methods:
- Review of current literature on programmed cell death.
- Analysis of molecular mechanisms and their functions.
- Evolutionary context application to cell death pathways.
Main Results:
- Programmed cell death pathways are more complex than previously thought.
- Cell suicide effectors have dual roles in death and survival.
- An evolutionary viewpoint reframes the understanding of cell death programs.
Conclusions:
- A 'bona fide' genetic death program may not exist in cells.
- Understanding the evolution of cell suicide offers therapeutic potential.
- Selection pressures on ancestral organisms shaped current cell death pathways.