A necrotic cell death model in a protist
A necrotic cell death model in a protist
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DOI：
10.1038/sj.cdd.4401994
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发表时间：
2007-02-01
影响因子：
12.4
通讯作者：
Golstein, P.
中科院分区：
文献类型：
--
作者：
Laporte, C.;Kosta, A.;Golstein, P.
虽然坏死性细胞死亡引起了相当大的兴趣，但其分子基础仍然知之甚少。在简单的生物模型中进行的研究，例如在动物王国之外进行的研究，可能受益于较少受到其他细胞死亡机制的干扰和更好的实验可及性，同时提供系统发育信息。坏死性细胞死亡能在动物界之外发生吗？在原生盘基骨柱中，发育刺激诱导自噬突变体产生一系列典型的坏死细胞死亡事件。该序列包括线粒体与线粒体2',7'-二氯荧光素双乙酸荧光的快速解偶联，ATP耗尽和氧气消耗增加。随后是扩大的线粒体在核周围聚集。随后质膜发生快速破裂，可通过延时录像和流式细胞仪进行量化。更有趣的是，发育刺激和经典的线粒体解偶联剂触发了类似的事件序列，外源性葡萄糖以非糖酵解的方式延迟了质膜破裂。原生动物盘基骨柱中坏死细胞死亡的发生(1)为进一步研究这种类型的细胞死亡提供了非常有利的模型，(2)强烈表明，坏死细胞死亡的机制存在于阿米巴原虫原生生物和动物共同的祖先中，并在进化中被保守。
While necrotic cell death is attracting considerable interest, its molecular bases are still poorly understood. Investigations in simple biological models, taken for instance outside the animal kingdom, may benefit from less interference from other cell death mechanisms and from better experimental accessibility, while providing phylogenetic information. Can necrotic cell death occur outside the animal kingdom? In the protist Dictyostelium, developmental stimuli induced in an autophagy mutant a stereotyped sequence of events characteristic of necrotic cell death. This sequence included swift mitochondrial uncoupling with mitochondrial 2',7'-dichlorofluorescein diacetate fluorescence, ATP depletion and increased oxygen consumption. This was followed by perinuclear clustering of dilated mitochondria. Rapid plasma membrane rupture then occurred, which was evidenced by time-lapse videos and quantified by FACS. Of additional interest, developmental stimuli and classical mitochondrial uncouplers triggered a similar sequence of events, and exogenous glucose delayed plasma membrane rupture in a nonglycolytic manner. The occurrence of necrotic cell death in the protist Dictyostelium ( 1) provides a very favorable model for further study of this type of cell death, and ( 2) strongly suggests that the mechanism underlying necrotic cell death was present in an ancestor common to the Amoebozoa protists and to animals and has been conserved in evolution.