Nature Medicine11, 725 - 730 (2005)
Published online: 6 July 2005; | doi:10.1038/nm1263
Caspase-independent cell death
Guido Kroemer1
& Seamus J Martin2
1
Centre National de la Recherche Scientifique, UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
2
Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Correspondence should be addressed to Guido Kroemer kroemer@igr.fr
Caspase activation has been frequently viewed as synonymous with apoptotic cell death; however, caspases can also contribute to processes that do not culminate in cell demise. Moreover, inhibition of caspases can have cytoprotective effects. In a number of different models, caspase inhibition does not maintain cellular viability and instead shifts the morphology of death from apoptosis to nonapoptotic pathways. Here, we explore the contribution of caspases to cell death, either as upstream signals or as downstream effectors contributing to apoptotic morphology, as well as alternative strategies for cell death inhibition. Such alternative strategies may either target catabolic hydrolases or be aimed at preventing mitochondrial membrane permeabilization and its upstream triggers.
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