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From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany

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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• Du, L., Zhang, X., Han, Y. Y., Burke, N. A., Kochanek, P. M., Watkins, S. C., Graham, S. H., Carcillo, J. A., Szabo, C., Clark, R. S. B. (2003). Intra-mitochondrial Poly(ADP-ribosylation) Contributes to NAD+ Depletion and Cell Death Induced by Oxidative Stress. J. Biol. Chem. 278: 18426-18433 [Abstract] [Full Text]  
• Munoz-Pinedo, C., Ruiz-Ruiz, C., Ruiz de Almodovar, C., Palacios, C., Lopez-Rivas, A. (2003). Inhibition of Glucose Metabolism Sensitizes Tumor Cells to Death Receptor-triggered Apoptosis through Enhancement of Death-inducing Signaling Complex Formation and Apical Procaspase-8 Processing. J. Biol. Chem. 278: 12759-12768 [Abstract] [Full Text]  
• Li, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B., Melendez, J. A., Robinson, J. P. (2003). Mitochondrial Complex I Inhibitor Rotenone Induces Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species Production. J. Biol. Chem. 278: 8516-8525 [Abstract] [Full Text]  
• Dussmann, H., Rehm, M., Kogel, D., Prehn, J. H. M. (2003). Outer mitochondrial membrane permeabilization during apoptosis triggers caspase-independent mitochondrial and caspase-dependent plasma membrane potential depolarization: a single-cell analysis. J. Cell Sci. 116: 525-536 [Abstract] [Full Text]  
• Ono, K., Kim, S. O., Han, J. (2003). Susceptibility of Lysosomes to Rupture Is a Determinant for Plasma Membrane Disruption in Tumor Necrosis Factor Alpha-Induced Cell Death. Mol. Cell. Biol. 23: 665-676 [Abstract] [Full Text]  
• Duan, S., Hajek, P., Lin, C., Shin, S. K., Attardi, G., Chomyn, A. (2003). Mitochondrial Outer Membrane Permeability Change and Hypersensitivity to Digitonin Early in Staurosporine-induced Apoptosis. J. Biol. Chem. 278: 1346-1353 [Abstract] [Full Text]  
• Manabat, C., Han, B.H., Wendland, M., Derugin, N., Fox, C.K., Choi, J., Holtzman, D.M., Ferriero, D.M., Vexler, Z.S. (2003). Reperfusion Differentially Induces Caspase-3 Activation in Ischemic Core and Penumbra After Stroke in Immature Brain. Stroke 34: 207-213 [Abstract] [Full Text]  
• Chandra, D., Liu, J.-W., Tang, D. G. (2002). Early Mitochondrial Activation and Cytochrome c Up-regulation during Apoptosis. J. Biol. Chem. 277: 50842-50854 [Abstract] [Full Text]  
• Terminella, C., Tollefson, K., Kroczynski, J., Pelli, J., Cutaia, M. (2002). Inhibition of apoptosis in pulmonary endothelial cells by altered pH, mitochondrial function, and ATP supply. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L1291-L1302 [Abstract] [Full Text]  
• Obrero, M., Yu, D. V., Shapiro, D. J. (2002). Estrogen Receptor-dependent and Estrogen Receptor-independent Pathways for Tamoxifen and 4-Hydroxytamoxifen-induced Programmed Cell Death. J. Biol. Chem. 277: 45695-45703 [Abstract] [Full Text]  
• Duan, L., Gan, H., Golan, D. E., Remold, H. G. (2002). Critical Role of Mitochondrial Damage in Determining Outcome of Macrophage Infection with Mycobacterium tuberculosis. J. Immunol. 169: 5181-5187 [Abstract] [Full Text]  

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