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.
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21 April 1997
Brief Definitive Report|
April 21 1997
Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis
Marcel Leist,
Marcel Leist
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
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Barbara Single,
Barbara Single
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
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Anna F. Castoldi,
Anna F. Castoldi
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
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Simone Kühnle,
Simone Kühnle
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
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Pierluigi Nicotera
Pierluigi Nicotera
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
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Marcel Leist
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
Barbara Single
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
Anna F. Castoldi
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
Simone Kühnle
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
Pierluigi Nicotera
From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany
Address correspondence to Professor P. Nicotera, Chair of Molecular Toxicology, University of Konstanz, POB 5560-X911, D-78457 Konstanz, Germany.
Received:
December 02 1996
Revision Received:
February 11 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (8): 1481–1486.
Article history
Received:
December 02 1996
Revision Received:
February 11 1997
Citation
Marcel Leist, Barbara Single, Anna F. Castoldi, Simone Kühnle, Pierluigi Nicotera; Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis. J Exp Med 21 April 1997; 185 (8): 1481–1486. doi: https://doi.org/10.1084/jem.185.8.1481
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