Tait, S.W.G. et al. (2013) Widespread mitochondrial depletion via mitophagy does not compromise necroptosis. Cell Reports, 5(4), pp. 878-885. (doi: 10.1016/j.celrep.2013.10.034) (PMID:24268776) (PMCID:PMC4005921)
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Abstract
Programmed necrosis (or necroptosis) is a form of cell death triggered by the activation of receptor interacting protein kinase-3 (RIPK3). Several reports have implicated mitochondria and mitochondrial reactive oxygen species (ROS) generation as effectors of RIPK3-dependent cell death. Here, we directly test this idea by employing a method for the specific removal of mitochondria via mitophagy. Mitochondria-deficient cells were resistant to the mitochondrial pathway of apoptosis, but efficiently died via tumor necrosis factor (TNF)-induced, RIPK3-dependent programmed necrosis or as a result of direct oligomerization of RIPK3. Although the ROS scavenger butylated hydroxyanisole (BHA) delayed TNF-induced necroptosis, it had no effect on necroptosis induced by RIPK3 oligomerization. Furthermore, although TNF-induced ROS production was dependent on mitochondria, the inhibition of TNF-induced necroptosis by BHA was observed in mitochondria-depleted cells. Our data indicate that mitochondrial ROS production accompanies, but does not cause, RIPK3-dependent necroptotic cell death.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Ichim, Dr Gabriel and Haller, Ms Martina and Tait, Professor Stephen and Karvela, Miss Maria |
| Authors: | Tait, S.W.G., Oberst, A., Quarato, G., Milasta, S., Haller, M., Wang, R., Karvela, M., Ichim, G., Yatim, N., Albert, M.L., Kidd, G., Wakefield, R., Frase, S., Krautwald, S., Linkermann, A., and Green, D.R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cell Reports |
| Publisher: | Elsevier Inc. |
| ISSN: | 2211-1247 |
| ISSN (Online): | 2211-1247 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in Cell Reports 5(4):878-885 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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