Intracellular adenosine triphosphate (ATP) concentration: A switch in the decision between apoptosis and necrosis

被引:1577
作者
Leist, M [1 ]
Single, B [1 ]
Castoldi, AF [1 ]
Kuhnle, S [1 ]
Nicotera, P [1 ]
机构
[1] UNIV KONSTANZ,CHAIR MOL TOXICOL,FAC BIOL,DEPT MOL TOXICOL,D-78457 CONSTANCE,GERMANY
关键词
D O I
10.1084/jem.185.8.1481
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
引用
收藏
页码:1481 / 1486
页数:6
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