No death without life: Vital functions of apoptotic effectors

L. Galluzzi, N. Joza, E. Tasdemir, M. C. Maiuri, M. Hengartner, J. M. Abrams, N. Tavernarakis, J. Penninger, F. Madeo, G. Kroemer

Research output: Contribution to journalReview articlepeer-review

199 Scopus citations

Abstract

As a result of the genetic experiments performed in Caenorhabditis elegans, it has been tacitly assumed that the core proteins of the 'apoptotic machinery' (CED-3, -4, -9 and EGL-1) would be solely involved in cell death regulation/execution and would not exert any functions outside of the cell death realm. However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. Similarly, loss-of-function mutations of ced-4 compromise the mitotic arrest of DNA-damaged germline cells from adult nematodes, even in a context in which the apoptotic machinery is inoperative (for instance due to mutations of egl-1 or ced-3). Moreover, EGL-1 is required for the activation of autophagy in starved nematodes. Finally, the depletion of caspase-independent death effectors, such as apoptosis-inducing factor (AIF) and endonuclease G, provokes cell death-independent consequences, both in mammals and in yeast (Saccharomyces cerevisiae). These results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosis-unrelated function, most likely as part of an adaptive response to cellular stress.

Original languageEnglish (US)
Pages (from-to)1113-1123
Number of pages11
JournalCell Death and Differentiation
Volume15
Issue number7
DOIs
StatePublished - Jul 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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