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The ATP Switch in Apoptosis

  • David J. McConkey
Chapter
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Conclusions

As a result of the work outlined above and other studies, a clear-cut distinction between apoptosis and necrosis no longer exists at the biochemical level. The strongest evidence for overlap comes from studies in models of hypoxia showing that over-expression of Bcl2 or its homolog Bcl-xL can block necrosis. The effects of Bcl2 appear largely due to direct effects on mitochondria, including stabilization of membrane potential, preservation of ATP production, prevention of oxidative stress, and enhanced Ca2+ uptake. In addition, Bcl2 may exert similar effects on the ER and the nucleus by regulating Ca2+ and GSH fluxes. If Bcl2 is not linked solely to suppression of apoptosis, what molecular distinctions between apoptosis and necrosis are we left with? A particularly attractive conclusion is that apoptosis requires caspases whereas necrosis does not (Hirsch et al., 1997). This would explain the ATP requirement for apoptosis, because Apaf-1-mediated activation of caspase-9-requires ATP hydrolysis (Li et al., 1997), and oxidation of the caspase active site cysteine would explain why excessive oxidative stress or thiol depletion inhibit apoptosis and lead to necrosis. It should be noted, however, that viral caspase inhibitors (such as the cowpox virus crmA protein) can partially attenuate necrosis that is due to chemical hypoxia (Shimizu et al., 1996a, 1996b). Further work is needed to directly examine the activation status of particular caspases in additional models of necrosis.

Keywords

Programme Cell Death Mitochondrial Permeability Transition Necrotic Cell Death Mitochondrial Transmembrane Potential Buthionine Sulfoximine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • David J. McConkey
    • 1
  1. 1.Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, and Program in ToxicologyUniversity of Texas-Houston Graduate School of Biomedical SciencesHouston

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