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Dev Cell,
2017]
Caspases have apoptotic and non-apoptotic functions, both of which depend on their abilities to cleave proteins at specific sites. What distinguishes apoptotic from non-apoptotic substrates has so far been unclear. In this issue of Developmental Cell, Weaver etal. (2017) now provide an answer to this crucial question.
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Nature Cell Biology,
2002]
Phagocytes have long been known to engulf and degrade apoptotic cells. Recent studies in mammals and the nematode Caenorhabditis elegans have shed some light on the conserved molecular mechanisms involved in this process. A series of results now challenge the traditional view of phagocytes as simply scavengers, 'cleaning up' after apoptosis to prevent inflammatory responses, and hence tissue damage. Instead, they suggest that phagocytes are active in the induction and/or execution of apoptosis in
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Annu Rev Genet,
2009]
The elimination of unwanted cells by programmed cell death is a common feature of animal development. Genetic studies in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have not only revealed the molecular machineries that cause the programmed demise of specific cells, but have also allowed us to get a glimpse of the types of pathways that regulate these machineries during development. Rather than serving as a broad overview of programmed cell death during development, this review focuses on recent advances in our understanding of the regulation of specific programmed cell death events during nematode, fly, and mouse development. Recent studies have revealed that many of the regulatory pathways involved play additional important roles in development, which confirms that the programmed cell death fate is an integral aspect of animal development.
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Ernst Schering Res Found Workshop,
2000]
The proliferation of cells is an integral part of development and tissue homeostatsis in multicellular animals(reviewed by Raff 1996; Folletee and O'farrel 1997). Two opposing processes, the division of cells on one hand and the programmed death of cells on the other hand, determine the overall rate of cell proliferation, The proper regulation of these two physiological processes is therefore a crucial aspect of development and of tissue homeostatsis(reviewed by Edgar and Lehner 1996; Shrr 1997;Jacobson et al. 1997). While the importance of the process of cell division has long been recognized, the role and extent of programmed cell death, or apoptosis, has only been realized within the last decades (Glucksmann 1950; Kerr et al. 19972). Massive programmed cell death occurs, for instance, during the development of the nervous system and in the immune system: more than 50% on all neurons and oligodendrocytes formed in the periperal and central vertebrate nervous system undergo programmed cell death neurogenesis...
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Cell Death Differ,
2016]
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Oncogene,
2008]
Since the discovery of mammalian BIK and BAD in 1995, BH3-only proteins have emerged as key activators of apoptotic cell death in animals as diverse as the nematode, Caenorhabditis elegans, and humans. BH3-only proteins have also emerged as integrators of cell-death signals that determine the life-versus-death decision and that transduce this decision to the central apoptotic machinery through their physical interaction with 'core' BCL-2 family members, such as BCL-2 or BCL-XL. Currently, eight BH3-only proteins have been identified and characterized in mammals, and there is evidence of functional overlap between them. In contrast, only two BH3-only proteins have so far been identified and characterized in C. elegans, EGL-1 and CED-13, and there seems to be only limited functional overlap between them. Combined with the powerful genetic tools available for the analysis of apoptosis in C. elegans, and the ability to study apoptosis at single-cell resolution in this organism, the absence of extensive functional redundancy makes C. elegans an ideal model for studies on BH3-only proteins. In this study, we will review our current understanding of the role and regulation of EGL-1. We will also briefly summarize studies on CED-13, which was identified more recently.
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Curr Opin Cell Biol,
2010]
Mitochondria are highly dynamic organelles that constantly fuse and divide. Dynamin-related GTPases are the core components of the machineries that mediate mitochondrial fusion and fission. The role and regulation of these machineries are currently under intense investigation. Recently, members of the BCL2 family of proteins, conserved regulators of apoptosis, have been implicated in the regulation of mitochondrial dynamics. Here, we review the functions of mitochondrial fusion and fission in apoptotic and nonapoptotic cells and how members of the BCL2 family of proteins regulate these functions.
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Cell,
1999]
Cell death in universally important in development, not the least in the nervous system, but little is known about how the programmed cell deaths of cells and neurons are ultimately controlled. Much of the understanding of cell death has come from research on the nematode Caenorhabditis elegans (reviewed by Metzstein et al., 1998). Conradt and Horvitz (1999 [this issue of Cell]) now extend this work to provide a satisfyingly complete explanation for the sex-specific death of one particular neuron type in this animal. In so doing, they link up two extensively studied regulatory pathways in C. elegans, one controlling sexual phenotype, and one controlling cell death.
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Curr Biol,
2005]
Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode''''s Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during
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Biochim Biophys Acta,
2011]
Although mitochondria are essential organelles for long-term survival of eukaryotic cells, recent discoveries in biochemistry and genetics have advanced our understanding of the requirements for mitochondria in cell death. Much of what we understand about cell death is based on the identification of conserved cell death genes in Drosophila melanogaster and Caenorhabditis elegans. However, the role of mitochondria in cell death in these models has been much less clear. Considering the active role that mitochondria play in apoptosis in mammalian cells, the mitochondrial contribution to cell death in non-mammalian systems has been an area of active investigation. In this article, we review the current research on this topic in three non-mammalian models, C. elegans, Drosophila, and Saccharomyces cerevisiae. In addition, we discuss how non-mammalian models have provided important insight into the mechanisms of human disease as they relate to the mitochondrial pathway of cell death. The unique perspective derived from each of these model systems provides a more complete understanding of mitochondria in programmed cell death. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.