Granzyme B-induced mitochondrial ROS are required for apoptosis
| العنوان: | Granzyme B-induced mitochondrial ROS are required for apoptosis |
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| المؤلفون: | Guillaume Jacquemin, Atsuko Kasahara, Jerome Thiery, Esen Yonca Bassoy, Denis Martinvalet, Judy Lieberman, Michael Walch, D. Margiotta |
| المصدر: | Cell Death & Differentiation. 22:862-874 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Oxidoreductase complex, Mitochondrial ROS, Original Paper, Electron Transport Complex I, NDUFS1, NDUFS2, Respiratory chain, Apoptosis, Cell Biology, Mitochondrion, Biology, Granzymes, Mitochondria, Rats, Cell biology, Animals, Electron Transport Complex III, Humans, K562 Cells, Mitochondrial Membranes, Reactive Oxygen Species, Molecular Biology, Granzyme B |
| الوصف: | Caspases and the cytotoxic lymphocyte protease granzyme B (GB) induce reactive oxygen species (ROS) formation, loss of transmembrane potential and mitochondrial outer membrane permeabilization (MOMP). Whether ROS are required for GB-mediated apoptosis and how GB induces ROS is unclear. Here, we found that GB induces cell death in an ROS-dependent manner, independently of caspases and MOMP. GB triggers ROS increase in target cell by directly attacking the mitochondria to cleave NDUFV1, NDUFS1 and NDUFS2 subunits of the NADH: ubiquinone oxidoreductase complex I inside mitochondria. This leads to mitocentric ROS production, loss of complex I and III activity, disorganization of the respiratory chain, impaired mitochondrial respiration and loss of the mitochondrial cristae junctions. Furthermore, we have also found that GB-induced mitocentric ROS are necessary for optimal apoptogenic factor release, rapid DNA fragmentation and lysosomal rupture. Interestingly, scavenging the ROS delays and reduces many of the features of GB-induced death. Consequently, GB-induced ROS significantly promote apoptosis. |
| تدمد: | 1476-5403 1350-9047 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::032d0285140d3757a198f121ccc4fd11 https://doi.org/10.1038/cdd.2014.180 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....032d0285140d3757a198f121ccc4fd11 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765403 13509047 |
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