دورية أكاديمية
Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation.
| العنوان: | Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. |
|---|---|
| المؤلفون: | Rogers, Corey, Erkes, Dan A., Nardone, Alexandria, Aplin, Andrew E., Fernandes-Alnemri, Teresa, Alnemri, Emad S. |
| المصدر: | Department of Biochemistry and Molecular Biology Faculty Papers |
| بيانات النشر: | Jefferson Digital Commons |
| سنة النشر: | 2019 |
| المجموعة: | Jefferson Digital Commons (Thomas Jefferson University, Philadelphia) |
| مصطلحات موضوعية: | Animals, Caspase 3, Cytochromes c, Fibroblasts, Gene Knockout Techniques, HEK293 Cells, HeLa Cells, Humans, Inflammasomes, Macrophages, Melanoma, Experimental, Mice, Inbred C57BL, Knockout, Mitochondria, Mitochondrial Membranes, Mutation, Phosphorylation, Primary Cell Culture, Protein Domains, Pyroptosis, Receptors, Estrogen, Skin Neoplasms, Threonine, Medical Biochemistry, Medical Molecular Biology, Medicine and Health Sciences |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://jdc.jefferson.edu/bmpfp/150Test; https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1150&context=bmpfpTest |
| الإتاحة: | https://jdc.jefferson.edu/bmpfp/150Test https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1150&context=bmpfpTest |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.FC6383 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |