Granzyme B-induced mitochondrial ROS are required for apoptosis
| Autor: | Guillaume Jacquemin, Atsuko Kasahara, Jerome Thiery, Esen Yonca Bassoy, Denis Martinvalet, Judy Lieberman, Michael Walch, D. Margiotta |
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| Rok vydání: | 2014 |
| Předmět: |
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 |
| Zdroj: | Cell Death & Differentiation. 22:862-874 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2014.180 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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