Ameisen J C
EMI-U 9922 INSERM/Université Paris 7, IFR 02, Hôpital Bichat-Claude Bernard, AP-HP, 46 rue Henri Huchard, 75877 Paris cedex 18, France.
Cell Death Differ. 2002 Apr;9(4):367-93. doi: 10.1038/sj.cdd.4400950.
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.
程序性细胞死亡是一种由基因调控的细胞自杀过程，对多细胞生物的发育、体内平衡和完整性至关重要。相反，控制细胞自杀的机制失调在多种疾病的发病机制中起作用。虽然在揭示程序性细胞死亡的分子机制方面已经取得了很大进展，但一个具有重要治疗意义的新的复杂层面已经开始显现，这表明：（i）我们细胞中可能存在几种不同的自我毁灭途径并并行运作；（ii）细胞自杀的分子效应器也可能执行其他与诱导细胞死亡无关但对细胞存活至关重要的功能。在这篇综述中，我将论证，当从进化背景来考虑时，这个新的复杂层面（意味着我们细胞中可能不存在“真正的”基因死亡程序）可能会得到更好的理解。当人们试图在祖先单细胞生物层面提出调控细胞自杀途径在进化过程中何时以及如何被选择的问题时，就会出现对调控细胞自杀途径的新观点。
