Stress-induced germ cell apoptosis by a p53 independent pathway in Caenorhabditis elegans

Salinas, Laura S.; Maldonado, Ernesto; Navarro, Rosa E.

doi:10.1038/sj.cdd.4401976

Cited by 99 publications

(118 citation statements)

References 35 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…In C. elegans, the evolutionarily conserved DNA damage-signaling network activates DNA repair and cell cycle checkpoints, but it does not activate caspase-dependent apoptosis in somatic cells. In this organism, genotoxins activate caspase-dependent apoptosis only in the germ cells [21][22][23]. Therefore, the DNA damage response pathways of C. elegans provide strong evidence for the statement that DNA damage does not always induce programmed cell death.…”

Section: Activation Of Caspase-dependent Apoptosis By Dna Damagementioning

confidence: 99%

DNA damage-induced cell death: lessons from the central nervous system

2007

View full text Add to dashboard Cite

npg DNA damage can, but does not always, induce cell death. While several pathways linking DNA damage signals to mitochondria-dependent and -independent death machineries have been elucidated, the connectivity of these pathways is subject to regulation by multiple other factors that are not well understood. We have proposed two conceptual models to explain the delayed and variable cell death response to DNA damage: integrative surveillance versus autonomous pathways. In this review, we discuss how these two models may explain the in vivo regulation of cell death induced by ionizing radiation (IR) in the developing central nervous system, where the death response is regulated by radiation dose, cell cycle status and neuronal development.

show abstract

Section: Activation Of Caspase-dependent Apoptosis By Dna Damagementioning

confidence: 99%

DNA damage-induced cell death: lessons from the central nervous system

2007

View full text Add to dashboard Cite

show abstract

“…Germ cell apoptosis is a key element to protect gonads from starvation, as exhibited by mutants of the caspase CED-3 that are unable to restore fertility after adult diapause (1). Previously, we found that starvation triggers germ cell apoptosis (3), and in this study we proposed a model to explain how this response is regulated in C. elegans.…”

mentioning

confidence: 90%

LIN-35/Rb Causes Starvation-Induced Germ Cell Apoptosis via CED-9/Bcl2 Downregulation in Caenorhabditis elegans

Lascarez-Lagunas

Silva-García

Dinkova

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

Apoptosis is an important mechanism for maintaining germ line health. In Caenorhabditis elegans, germ cell apoptosis occurs under normal conditions to sustain gonad homeostasis and oocyte quality. Under stress, germ cell apoptosis can be triggered via different pathways, including the following: (i) the CEP-1/p53 pathway, which induces germ cell apoptosis when animals are exposed to DNA damage; (ii) the mitogen-activated protein kinase kinase (MAPKK) pathway, which triggers germ cell apoptosis when animals are exposed to heat shock, oxidative stress, or osmotic stress; and (iii) an unknown mechanism that triggers germ cell apoptosis during starvation. Here, we address how starvation induces germ cell apoptosis. Using polysomal profiling, we found that starvation for 6 h reduces the translationally active ribosomes, which differentially affect the mRNAs of the core apoptotic machinery and some of its regulators. During starvation, lin-35/Rb mRNA increases its expression, resulting in the accumulation of this protein. As a consequence, LIN-35 downregulates the expression of the antiapoptotic gene ced-9/Bcl-2. We observed that the reduced translation of ced-9/Bcl-2 mRNA during food deprivation together with its downregulation drastically affects its protein accumulation. We propose that CED-9/Bcl-2 downregulation via LIN-35/Rb triggers germ cell apoptosis in C. elegans in response to starvation. Many germ cells (known in many organisms as nurse cells) are needed to produce a single oocyte. Once they have served their purpose, nurse cells are eliminated by apoptosis. An unsolved question in the germ cell field is how apoptosis is triggered to produce and sometimes protect germ cells. Adult Caenorhabditis elegans nematodes that encounter food deprivation enter a diapause stage that allows them to survive for a few months and put off fertility (1, 2). Later, when animals are subjected to better conditions, they exit adult diapause and restore fertility. Germ cell apoptosis is a key element to protect gonads from starvation, as exhibited by mutants of the caspase CED-3 that are unable to restore fertility after adult diapause (1). Previously, we found that starvation triggers germ cell apoptosis (3), and in this study we proposed a model to explain how this response is regulated in C. elegans.In C. elegans, apoptosis occurs in somatic tissues during embryonic and postembryonic development (developmental apoptosis) (4, 5) and in the adult hermaphrodite gonad (physiological germ cell apoptosis) (6). In this nematode, apoptosis is executed via a conserved pathway that consists of the proteins CED-3 (a caspase), CED-4 (APAF1-like adaptor protein), and CED-9 (BCL2 ortholog) (reviewed in references 7 and 8). Developmental apoptosis is initiated when the protein EGL-1 (BH3-only) disrupts the CED-9/CED-4 complex, thereby triggering CED-3 activation.The mechanism that induces physiological germ cell apoptosis is independent of EGL-1 (6) and is partially induced by the ortholog of the human retinoblastoma gene (Rb) lin-35, which...

show abstract

“…Alternatively, apoptosis might be part of the mechanism that allows worms to quickly adapt to maintain germ cell homeostasis in response to environmental challenges. The observed increase of germ cell apoptosis upon starvation makes sense to focus limited resources to ensure the survival of some oocytes (which are post-pachytene and thus cannot undergo apoptosis) at the expense of culling pachytene cells (Salinas et al 2006 ;Angelo and Van Gilst 2009 ) . Since mitotic germ stem cells do not have the potential to die by apoptosis, down-regulation of germ cell proliferation would still waste the majority of later germ cells if limiting resources were equally distributed amongst developing oocytes.…”

Section: Why Do Cells Die By Physiological Germ Cell Apoptosis and Evmentioning

confidence: 99%

“…At present we know most about DNA damage response pathways leading to apoptosis. Finally, stresses such as starvation, heat shock, bacterial infection, or a high glucose diet also trigger excessive germ cell apoptosis (Salinas et al 2006 ;Angelo and Van Gilst 2009 ;Aballay and Ausubel 2001 ;Choi 2011 ) .…”

Section: Introductionmentioning

confidence: 99%

Germ Cell Apoptosis and DNA Damage Responses

Bailly

Gartner

2012

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

In the past 12 years, since the fi rst description of C. elegans germ cell apoptosis, this area of research rapidly expanded. It became evident that multiple genetic pathways lead to the apoptotic demise of germ cells. We are only beginning to understand how these pathways that all require the CED-9/Bcl-2, Apaf-1/CED-4 and CED-3 caspase core apoptosis components are regulated. Physiological apoptosis, which likely accounts for the elimination of more than 50% of all germ cells, even in unperturbed conditions, is likely to be required to maintain tissue homeostasis. The best-studied pathways lead to DNA damage-induced germ cell apoptosis in response to a variety of genotoxic stimuli. This apoptosis appears to be regulated similar to DNA damage-induced apoptosis in the mouse germ line and converges on p53 family transcription factors. DNA damage response pathways not only lead to apoptosis induction, but also directly affect DNA repair, and a transient cell cycle arrest of mitotic germ cells. Finally, distinct pathways activate germ cell apoptosis in response to defects in meiotic recombination and meiotic chromosome pairing.

show abstract

Stress-induced germ cell apoptosis by a p53 independent pathway in Caenorhabditis elegans

Cited by 99 publications

References 35 publications

DNA damage-induced cell death: lessons from the central nervous system

DNA damage-induced cell death: lessons from the central nervous system

LIN-35/Rb Causes Starvation-Induced Germ Cell Apoptosis via CED-9/Bcl2 Downregulation in Caenorhabditis elegans

Germ Cell Apoptosis and DNA Damage Responses

Contact Info

Product

Resources

About