Abstract
While necrotic cell death is attracting considerable interest, its molecular bases are still poorly understood. Investigations in simple biological models, taken for instance outside the animal kingdom, may benefit from less interference from other cell death mechanisms and from better experimental accessibility, while providing phylogenetic information. Can necrotic cell death occur outside the animal kingdom? In the protist Dictyostelium, developmental stimuli induced in an autophagy mutant a stereotyped sequence of events characteristic of necrotic cell death. This sequence included swift mitochondrial uncoupling with mitochondrial 2′,7′-dichlorofluorescein diacetate fluorescence, ATP depletion and increased oxygen consumption. This was followed by perinuclear clustering of dilated mitochondria. Rapid plasma membrane rupture then occurred, which was evidenced by time-lapse videos and quantified by FACS. Of additional interest, developmental stimuli and classical mitochondrial uncouplers triggered a similar sequence of events, and exogenous glucose delayed plasma membrane rupture in a nonglycolytic manner. The occurrence of necrotic cell death in the protist Dictyostelium (1) provides a very favorable model for further study of this type of cell death, and (2) strongly suggests that the mechanism underlying necrotic cell death was present in an ancestor common to the Amoebozoa protists and to animals and has been conserved in evolution.
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Abbreviations
- CCCP:
-
carbonyl cyanide 3-chlorophenylhydrazone
- DC-FDA:
-
2′,7′-dichlorofluorescein diacetate
- DIF:
-
differentiation-inducing factor
- DNP:
-
dinitrophenol
- 2-DOG:
-
2-deoxyglucose
- PI:
-
propidium iodide
- VDAC:
-
voltage-dependent anion channel
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Acknowledgements
We thank INSERM and CNRS for institutional support, and for specific grants Agence Nationale pour la Recherche (DictyDeath ANR-05-BLAN-0333-01), the European Community (FP6 STREP TransDeath LSHG-CT-2004-511983), the Ministère pour la Recherche (ACI BCMS174), Cancéropôle PACA and Association pour la Recherche contre le Cancer. We thank Jonathan Ewbank, Didier Marguet, Pierre-Henri Puech and Gérard Brandolin for helpful discussions and reading the manuscript.
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Laporte, C., Kosta, A., Klein, G. et al. A necrotic cell death model in a protist. Cell Death Differ 14, 266–274 (2007). https://doi.org/10.1038/sj.cdd.4401994
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DOI: https://doi.org/10.1038/sj.cdd.4401994
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