Alternative cell death mechanisms in development and beyond

  1. Guido Kroemer2,3,4,5,6
  1. 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
  2. 2U848, INSERM, 92805 Villejuif, France;
  3. 3Metabolomics Platform, Institut Gustave Roussy, 92805 Villejuif, France;
  4. 4Centre de Recherche des Cordeliers, 75006 Paris, France;
  5. 5Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 750015 Paris, France;
  6. 6Université Paris Descartes, Paris 5, 75006 Villejuif, France

    Abstract

    A canonical regulatory pathway involving the members of the Bcl-2 and caspase families has been established to regulate developmental apoptosis in nematodes and flies. However, mutant mice that have major deficiencies in this apoptosis pathway show only relatively minor developmental defects. Recent revelations indicate that multiple mechanisms are involved in regulating cell death during mammalian development, tissue homeostasis, and pathological cell loss. Here, we critically evaluate the evidence demonstrating the existence of alternative cell death mechanisms, including apoptosis of lower organisms in the absence of canonical apoptosis mediators, autophagic cell death, necroptosis, elimination by shedding, keratinocyte death by cornification, and cell–cell cannibalism by entosis. The physiological relevance of alternative cell death mechanisms as primary and backup mechanisms is discussed.

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