Dataset Information

Widespread mitochondrial depletion via mitophagy does not compromise necroptosis.

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.

SUBMITTER: Tait SW

PROVIDER: S-EPMC4005921 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Widespread mitochondrial depletion via mitophagy does not compromise necroptosis.

Tait Stephen W G SW Oberst Andrew A Quarato Giovanni G Milasta Sandra S Haller Martina M Wang Ruoning R Karvela Maria M Ichim Gabriel G Yatim Nader N Albert Matthew L ML Kidd Grahame G Wakefield Randall R Frase Sharon S Krautwald Stefan S Linkermann Andreas A Green Douglas R DR

Cell reports 20131121 4

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 ...[more]

PMID: 24268776

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Dataset Information

Widespread mitochondrial depletion via mitophagy does not compromise necroptosis.

Publications

Widespread mitochondrial depletion via mitophagy does not compromise necroptosis.

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