Depletion of Endonuclease G Selectively Kills Polyploid Cells

Büttner, Sabrina; Carmona-Gutiérrez, Didac; Vitale, Ilio; Castedo, Maria; Ruli, Doris; Eisenberg, Tobias; Kroemer, Guido; Madeo, Frank

doi:10.4161/cc.6.9.4218

Cited by 27 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 In fact, a vital role of EndoG in the maintenance of polyploid cells has been recently described for both yeast cells and human cancer cells. 78 In humans, mitochondrial fragmentation (fission) plays a causal role in apoptosis and is regulated by the dynaminrelated protein-1 (Drp1). Mitochondrial shape transitions are critical for yeast cell death, as well: for instance, upon challenge with diverse death stimuli, the yeast homolog of Drp1 (Dnm1p) promotes apoptosis preceded by mitochondrial fragmentation and degradation.…”

Section: Proteins and Pathways Regulating Yeast Apoptosismentioning

confidence: 99%

Apoptosis in yeast: triggers, pathways, subroutines

et al. 2010

View full text Add to dashboard Cite

A cell's decision to die is controlled by a sophisticated network whose deregulation contributes to the pathogenesis of multiple diseases including neoplastic and neurodegenerative disorders. The finding, more than a decade ago, that baker's yeast (Saccharomyces cerevisiae) can undergo apoptosis uncovered the possibility to investigate this mode of programmed cell death (PCD) in a model organism that combines both technical advantages and a eukaryotic 'cell room.' Since then, numerous exogenous and endogenous triggers have been found to induce yeast apoptosis and multiple yeast orthologs of crucial metazoan apoptotic regulators have been identified and characterized at the molecular level. Such apoptosis-relevant orthologs include proteases such as the yeast caspase as well as several mitochondrial and nuclear proteins that contribute to the execution of apoptosis in a caspase-independent manner. Additionally, physiological scenarios such as aging and failed mating have been discovered to trigger apoptosis in yeast, providing a teleological interpretation of PCD affecting a unicellular organism. Due to its methodological and logistic simplicity, yeast constitutes an ideal model organism that is efficiently helping to decipher the cell death regulatory network of higher organisms, including the switches between apoptotic, autophagic, and necrotic pathways of cellular catabolism. Here, we provide an overview of the current knowledge about the apoptotic subroutine of yeast PCD and its regulation.

show abstract

Section: Proteins and Pathways Regulating Yeast Apoptosismentioning

confidence: 99%

Apoptosis in yeast: triggers, pathways, subroutines

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Interestingly, it has been demonstrated that EndoG is required for the survival of tetraploid S. cerevisiae cells, an observation that was confirmed in tetraploid human colon cancer cell clones. 87 Finally, metacaspases (which may represent a phylogenetic ancestor of mammalian caspases) are not only implicated in various cell death scenarios, 143 but have been recently shown to modulate cell cycle progression and stress responses in fungal and protozoan models. 144,145 …”

Section: Day Jobs Of Night Killers L Galluzzi Et Almentioning

confidence: 99%

“…85 In accord with the observation that recombination-dependent DNA repair is essential for the survival of tetraploid cells, 86 EndoG knockdown causes the death of tetraploid tumor cells. 87 The stress-activated endoprotease Omi stress-regulated endoprotease (Omi) (also known as high temperature requirement protein A 2, i.e. HtrA2) belongs to a family of serine proteases that is well conserved from bacteria to humans.…”

Section: Vital Functions Of Mitochondrial Death Effectorsmentioning

confidence: 99%

No death without life: vital functions of apoptotic effectors

et al. 2008

View full text Add to dashboard Cite

As a result of the genetic experiments performed in Caenorhabditis elegans, it has been tacitly assumed that the core proteins of the 'apoptotic machinery' (CED-3, -4, -9 and EGL-1) would be solely involved in cell death regulation/execution and would not exert any functions outside of the cell death realm. However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. Similarly, loss-of-function mutations of ced-4 compromise the mitotic arrest of DNA-damaged germline cells from adult nematodes, even in a context in which the apoptotic machinery is inoperative (for instance due to mutations of egl-1 or ced-3). Moreover, EGL-1 is required for the activation of autophagy in starved nematodes. Finally, the depletion of caspaseindependent death effectors, such as apoptosis-inducing factor (AIF) and endonuclease G, provokes cell death-independent consequences, both in mammals and in yeast (Saccharomyces cerevisiae). These results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosisunrelated function, most likely as part of an adaptive response to cellular stress.

show abstract

“…EndoG is also thought to function in a non-apoptotic form of programmed cell death (21). Evidence for a positive function of EndoG in cell proliferation has been presented (8,22,23). A proposed role of mammalian EndoG in the genomic inversion of herpesvirus (22,24) suggests the possibility that not all of EndoG is sequestered in mitochondria.…”

mentioning

confidence: 99%

The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G

Temme

Weißbach

Lilie

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Endonuclease G (EndoG) is a mitochondrial enzyme believed to be released during apoptosis to participate in the degradation of nuclear DNA. This paper describes a Drosophila protein, EndoGI, which inhibits EndoG specifically. EndoG and EndoGI associate with subpicomolar affinity, forming a 2:1 complex in which dimeric EndoG is bound by two tandemly repeated homologous domains of monomeric EndoGI. Binding appears to involve the active site of EndoG. EndoGI is present in the cell nucleus at micromolar concentrations. Upon induction of apoptosis, levels of the inhibitor appear to be reduced, and it is relocalized to the cytoplasm. EndoGI, encoded by the predicted open reading frame cg4930, is expressed throughout Drosophila development. Flies homozygous for a hypomorphic EndoGI mutation have a strongly reduced viability, which is modulated by genetic background and diet. We propose that EndoGI protects the cell against low levels of EndoG outside mitochondria.

show abstract

Depletion of Endonuclease G Selectively Kills Polyploid Cells

Cited by 27 publications

References 28 publications

Apoptosis in yeast: triggers, pathways, subroutines

Apoptosis in yeast: triggers, pathways, subroutines

No death without life: vital functions of apoptotic effectors

The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G

Contact Info

Product

Resources

About