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Genes Dev. 2016 Oct 1;30(19):2133-2151.

Interrogating the relevance of mitochondrial apoptosis for vertebrate development and postnatal tissue homeostasis.

Author information

1
Division of Developmental Immunology, Biocenter, Medical University Innsbruck, A6020 Innsbruck, Austria.
2
Institute of Pharmacology, University of Bern, Inselspital, CH3010 Bern, Switzerland.
3
Tyrolean Cancer Research Institute, A6020 Innsbruck, Austria.

Abstract

"Programmed cell death or 'apoptosis' is critical for organogenesis during embryonic development and tissue homeostasis in the adult. Its deregulation can contribute to a broad range of human pathologies, including neurodegeneration, cancer, or autoimmunity…" These or similar phrases have become generic opening statements in many reviews and textbooks describing the physiological relevance of apoptotic cell death. However, while the role in disease has been documented beyond doubt, facilitating innovative drug discovery, we wonder whether the former is really true. What goes wrong in vertebrate development or in adult tissue when the main route to apoptotic cell death, controlled by the BCL2 family, is impaired? Such scenarios have been mimicked by deletion of one or more prodeath genes within the BCL2 family, and gene targeting studies in mice exploring the consequences have been manifold. Many of these studies were geared toward understanding the role of BCL2 family proteins and mitochondrial apoptosis in disease, whereas fewer focused in detail on their role during normal development or tissue homeostasis, perhaps also due to an irritating lack of phenotype. Looking at these studies, the relevance of classical programmed cell death by apoptosis for development appears rather limited. Together, these many studies suggest either highly selective and context-dependent contributions of mitochondrial apoptosis or significant redundancy with alternative cell death mechanisms, as summarized and discussed here.

KEYWORDS:

BCL2 family; BH3-only proteins; cell death; development; tissue homeostasis

PMID:
27798841
PMCID:
PMC5088563
DOI:
10.1101/gad.289298.116
[Indexed for MEDLINE]
Free PMC Article

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