Keynote

The Siren's Song: This Death That Makes Life Live

  1. Gerry Melino1,
  2. Richard A Knight1,
  3. Jean-Claude Ameisen2

Published Online: 15 DEC 2009

DOI: 10.1002/9780470015902.a0021560

eLS

eLS

How to Cite

Melino, G., Knight, R. A. and Ameisen, J.-C. 2009. The Siren's Song: This Death That Makes Life Live. eLS. .

Author Information

  1. 1

    University of Leicester, MRC Toxicology Unit, Leicester, UK

  2. 2

    Université Paris 7, Faculté de Médecine, Xavier Bichat, Paris, France

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Individual cells can divide (mitosis), specialize (differentiate) or undergo programmed cell death (apoptosis). The balance between these processes ensures that the number of cells in an organism remains essentially constant. In the past 30 years, the molecular mechanisms of cell death have been identified (caspases, Bcl-2 family, death receptors and apoptosome), with their clinical implications and therapeutic exploitation. Here, we review the entire process from a philosophical and historical viewpoint.

Key Concepts:

  • Besides dividing (mitosis) and specializing (differentiation), cells have an inherent, genetically programmed and biochemically regulated molecular mechanism of programmed cell death.

  • Life is a result of a continuous suppression of this death mechanism. In fact this programmed cell death pathway is always ready, and can be activated within minutes by membrane (cell to cell communication), cytosolic (stress) or nuclear (DNA damage) events.

  • Different forms of programmed cell death have been described, requiring different molecular subroutines, and with different morphological phenotypes and which occur in specific tissues. These include, among others and in addition to apoptosis, autophagy, keratinization, Wallerian degeneration and megakaryocytic fragmentation.

  • In contrast to apoptosis (a programmed cell death requiring caspase enzymatic activation, mitochondrial/apoptosome activation and Bcl-2-family regulation), necrosis causes the nonregulated release of intracellular molecules, resulting in inflammation. Indeed, apoptosis is often a silent, rapid death occurring in minutes and leaving no trace.

  • The pharmacologic regulation of cell death will affect all those diseases in which there is too little cell death (e.g. cancer and viral infections) or too much cell death (e.g. neurodegeneration and AIDS). Therefore the identification of the molecular events underlying apoptosis could lead to novel therapeutic approaches.

Keywords:

  • apoptosis;
  • cell death;
  • caspases;
  • Bcl-2;
  • C. elegans;
  • P53