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Book Review |
edited by Michael D. Jacobson and Nicola McCarthy
Oxford University Press (2002) 321 pages. ISBN 0-19-9638497 £35
Life for cells in an organism is not as easy as you might think. Every cell that has a job and lives in harmony with its neighbours will receive its daily supply of vittles and other goodies to keep going until... homeostasis, that's the rule. Cells who do not want to follow the rule and have ideas of rebellion, beware: Big Brother is watching and will make sure that any offenders are quickly and silently removed. Apoptosis, they call it, and the offender will be required to participate. You need strong rules to maintain homeostasis, but the system has proved its worth.
Too little apoptosis is a cause of, or an aggravating factor in, cancer and autoimmune diseases. Too much apoptosis is not good either, as it may permanently inactivate a vital organ and lead to the collapse of a whole edifice, as is seen in degenerative diseases. However harsh the rule may seem, it is probably very important because it has been conserved and refined during evolution.
Although programmed cell death was first identified in the 1800s, its importance has been recognized only recently. Apoptosis has now become one of the most popular and prolific subjects of biomedical research. In this book, Jacobson and McCarthy have assembled a series of reviews in an attempt to capture the relevant and lasting ideas emanating from more than 100,000 scientific publications on the subject.
The chapter by McCarthy recapitulates the main facts about apoptosis, such as the morphological features, the different phases and the main players in that deadly game. The delineation of the molecular mechanisms of apoptosis owes much to genetic studies of the development of the C. elegans. Xue, Wu and Shah review the advantages of this system and how this simple worm has helped unravel most aspects of the apoptotic process, from the commitment point to the disposal of the corpses. Bergmann and Steller explain why Drosophila has been useful in the study of apoptosis: Drosophila are genetically accessible, like C. elegans, yet have developmental plasticity, like vertebrates. The death sentence is carried out by special proteases called caspases. Roy and Cardone recapitulate the many different aspects of caspase activation, and the different roles each individual caspase might play in this proteolytic cascade.
Two of the most fiercely debated issues in the study of apoptosis are the role that mitochondria may play and how the Bcl-2 family of proteins regulate the activation of caspases. It is widely accepted that the mitochondrial intermembrane space houses a number of extremely dangerous molecules (cytochrome c, caspases, Smac/Diablo, AIF) that are released into the cytoplasm at some point during the apoptotic process. The anti-apoptotic proteins of the Bcl-2 family inhibit this release, whereas the pro-apoptotic members favour it. Tsujimoto, Kroemer and Clarke have had the difficult task of extracting some definitive ideas out of a sea of condradictory results. What will remain of it in the long term is not clear. Such is the intensity of the research in this area that we could already write an addendum to supplement Tsujimoto's addendum. McCarthy and Bennet review the death pathway initiated by death receptors and their ligands, and Franke shows us how many different apoptotic and survival signals may be integrated by kinases and phosphatases.
Finally, and to justify all that frantic research on apoptosis, Vaux explains how the ongoing battle between cells and viruses has provided much insight into the molecular mechanisms of apoptosis, whereas Jacobson and Bergeron review the importance of apoptosis in the development of the nervous system and in neurodegenerative disorders, such as stroke or Alzheimer's disease. I would probably have welcomed a special chapter about the different diseases that are believed to be in part caused by the deregulation of an apoptotic pathway.
Overall, this book clearly meets the goals that were set by the editors, and recapitulates the fundamental findings about the general cell death machinery. It is definitely a valuable addition to the library of any newcomer to the field, and I would certainly recommend it to any undergraduate students joining our lab. However, this field is an extremely fast-moving one, and some ideas have a very short life. Thus, a warning should be issued that the content of this book should not be considered as the definitive truth in all regards, but rather as a collection of beliefs that are awaiting confirmation. This is quite normal after all, because an understanding of cell death is still very much in development. As for cells, death is the default pathway of scientific hypotheses. They need permanent input to stay alive, and most of the wrong ones contain the reasons for their own silent removal and oblivion. No doubt, with time, many of the now popular beliefs will undergo apoptosis and a more mature and stable consensus will remain. Homeostasis, at last...
The Walter and Eliza Hall Institute, P.O. The Royal Melbourne Hospital, Parkville, Victoria, Australia
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