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A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans

Nature Cell Biology volume 2, pages 931–937 (2000)Cite this article

Abstract

Similar to mammalian excitotoxic cell death, necrotic-like cell death (NCD) in Caenorhabditis elegans can be initiated by hyperactive ion channels. Here we investigate the requirements for genes that execute and regulate programmed cell death (PCD) in necrotic-like neuronal death caused by a toxic MEC-4 channel. Neither the kinetics of necrosis onset nor the total number of necrotic corpses generated is altered by any C. elegans mutation known to block PCD, which provides genetic evidence that the activating mechanisms for NCD and apoptotic cell death are distinct. In contrast, all previously reported ced genes required for phagocytotic removal of apoptotic corpses, as well as ced-12, a new engulfment gene we have identified, are required for efficient elimination of corpses generated by distinct necrosis-inducing stimuli. Our results show that a common set of genes acts to eliminate cell corpses irrespective of the mode of cell death, and provide the first identification of the C. elegans genes that are required for orderly removal of necrotic cells. As phagocytotic mechanisms seem to be conserved from nematodes to humans, our findings indicate that injured necrotic cells in higher organisms might also be eliminated before lysis through a controlled process of corpse removal, a hypothesis that has significant therapeutic implications.

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Figure 1: ced-9, egl-1, ced-3 and ced-4 do not affect mec-4(u231)-induced cell death.
Figure 2: Engulfment genes promote the removal of necrotic-like cell corpses.
Figure 3: ced-12 promotes the removal of both necrotic and apoptotic cell corpses.
Figure 4: Distinct cell-death processes generate corpses that are removed by a common engulfment mechanism.

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Acknowledgements

We thank R. Francis and T. Schedl for providing the oz167 allele. Some strains were provided by The Caenorhabditis Genetics Center, which is supported by the National Institute of Health National Center for Research Resources, M. Chalfie, D. Xue, R. Plasterk and H. R. Horvitz. We thank G. Patterson and members of the Driscoll laboratory for discussion and comments on the manuscript. This work was supported by NIH grants R01NS34435 (to M.D.) and GM-52540 (to M.O.H.); S.C. was supported in part by grant no. 5T32GM08360.

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Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, 604 Allison Road , Piscataway, 08854, New Jersey, USA

    Sambath Chung & Monica Driscoll

  2. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, 11724 , New York, USA

    Tina L. Gumienny & Michael O. Hengartner

  3. Program in Genetics, State University of New York at Stony Brook, Stony Brook, 11794, New York, USA

    Tina L. Gumienny & Michael O. Hengartner

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Correspondence to Monica Driscoll.

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Chung, S., Gumienny, T., Hengartner, M. et al. A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat Cell Biol 2, 931–937 (2000). https://doi.org/10.1038/35046585

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