Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 812K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sreenivasan, A. Search for Related Content PubMed Articles by Sreenivasan, A. Related Collections Related Articles Social Bookmarking                            What's this?

Zombie cells

The death of cells lacking some caspases is delayed but still inevitable.

Looks can be deceiving—even a cell that appears healthy may be doomed to die. Ekert et al. (page 835) report that cells lacking two important caspases can survive in the short term without a growth factor, but will succumb eventually. Thus, the normal job of these caspases may be to accelerate the dying process rather than control the commitment of cells to death.

The situation varies between organisms. In worms, deletion of CED-4 and CED-3 (the homologues of mammalian Apaf-1 and caspase-9) completely prevents programmed cell death. Some mice without Apaf-1 and caspase-9 die from neuronal overgrowth but others fare just fine. One possibility is that another caspase such as caspase-2 takes over when caspase-9 is absent or can't be activated by Apaf-1.

Ekert and colleagues used growth factor–dependent cell lines to study apoptosis when Apaf-1, caspase-9, or caspase-9 and -2 were missing. When deprived of the factor IL-3, none of the cells shrank, had blebbed membranes, or exhibited any other obvious apoptotic phenotypes. But closer examination revealed that, though normal to the naked eye, the cells had released cytochrome c from their mitochondria—a classic sign of apoptosis. To add insult to injury, the cells were essentially zombies. Even when IL-3 was restored to the medium they could not make clones. Marsden et al. (page 775) similarly find that lymphocytes and fibroblasts lacking caspase-2 and -9 remained sensitive to many apoptotic stimuli.

The cause of cell death in the caspase-deleted cells remains unclear. Mitochondrial ATP generation may be fatally compromised by the leakage of cytochrome c, another mitochondrial factor may leak out, or another caspase may initiate an irreversible event. Whatever the explanation, the current results suggest that the loss of certain caspases in cancer cells does not necessarily explain the increased survival of these cancer cells.

Aparna Sreenivasan

aparnas{at}nasw.org

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Articles

Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die

Paul G. Ekert, Stuart H. Read, John Silke, Vanessa S. Marsden, Hitto Kaufmann, Christine J. Hawkins, Robert Gerl, Sharad Kumar, and David L. Vaux
J. Cell Biol. 2004 165: 835-842. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 812K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sreenivasan, A. Search for Related Content PubMed Articles by Sreenivasan, A. Related Collections Related Articles Social Bookmarking                            What's this?