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

M Leist, B Single, AF Castoldi, S Kühnle… - The Journal of …, 1997 - rupress.org
M Leist, B Single, AF Castoldi, S Kühnle, P Nicotera
The Journal of experimental medicine, 1997rupress.org
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 …
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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