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We are analyzing https://www.nature.com/articles/s41467-019-09397-2.

Title:
Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation | Nature Communications
Description:
Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway. Gasdermins mediate lytic cell death by forming pores in the plasma membrane. Here the authors show that gasdermins also permeabilize mitochondrial membrane, thereby facilitating intrinsic apoptosis pathway, downstream of apoptotic (Gasdermin E) and inflammatory (Gasdermin D) caspase activation.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {πŸ”}

cells, gsdme, caspase, cell, fig, article, activation, google, scholar, mitochondria, cas, gsdmen, release, cyt, mitochondrial, death, apoptosis, cemc, media, membrane, pyroptosis, min, cat, activity, supplementary, apoptotic, expression, cancer, gsdmeko, nature, results, tumor, gsdmd, mutant, culture, proteins, gasdermin, pathway, gsdmeegfp, buffer, cleavage, active, lysates, pores, plasma, gsdma, shown, pyroptotic, immunoblots, response,

Topics {βœ’οΈ}

nature portfolio crispr/cas9 gene editing privacy policy excellent services crispr design tools advertising gene editing gsdme-n-egfp-expressing hek293t cells gsdme-t6e-expressing cem-c7 cells cells expressing gsdme-n-t6e-egfp thermo scientific nature communications commercial research grant 293t-gsdme-d270e-egfp cells transfected c-terminally truncated protein52 tgf-beta-dependent apoptotic signalling bone marrow-derived cells gsdme-n-egfp variants t6e gsdme-d270e-egfp cell lines time-lapse live-cell imaging cells expressing gsdme-n-egfp reprints bax/bak-mediated pore formation author information authors nf-kappab target genes 293t-gsdme-egfp-d270e cells cleaved gsdme-c-egfp domain positive feed-forward loop gsdme-ko cem-c7 cells amplifying feed-forward loop plasma membrane-pore-forming functions voltage-dependent anion channel mcherry-tagged mitochondrial htra2 high-molecular weight oligomers gfp-trap agarose beads tumor necrosis factor-Ξ± cem-c7 cell lines helaΒ cells stably reconstituted pre-mature stop codon op de beeck gsdme-n-mediated caspase-3 activation cem-c7 cells showed stably expressing gsdme-egfp gsdme-ko b16-ova cells gsdme-n-egfp showed full-length gsdme-egfp nature 526 nature 547 nature 535 nature 514

Questions {❓}

  • Mitochondrial DNA signals driving immune responses: Why, How, Where?

Schema {πŸ—ΊοΈ}

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         headline:Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation
         description:Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway. Gasdermins mediate lytic cell death by forming pores in the plasma membrane. Here the authors show that gasdermins also permeabilize mitochondrial membrane, thereby facilitating intrinsic apoptosis pathway, downstream of apoptotic (Gasdermin E) and inflammatory (Gasdermin D) caspase activation.
         datePublished:2019-04-11T00:00:00Z
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      headline:Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation
      description:Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway. Gasdermins mediate lytic cell death by forming pores in the plasma membrane. Here the authors show that gasdermins also permeabilize mitochondrial membrane, thereby facilitating intrinsic apoptosis pathway, downstream of apoptotic (Gasdermin E) and inflammatory (Gasdermin D) caspase activation.
      datePublished:2019-04-11T00:00:00Z
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      name:Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
      name:Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
      name:Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
      name:Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA

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