Widespread Mitochondrial Depletion Via Mitophagy Does Not Compromise Necroptosis

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2013 Nov 26

PMID 24268776

Citations 168

Authors

Stephen W G Tait

Andrew Oberst

Giovanni Quarato

Sandra Milasta

Martina Haller

Ruoning Wang

Maria Karvela

Gabriel Ichim

Nader Yatim

Matthew L Albert

Grahame Kidd

Randall Wakefield

Sharon Frase

Stefan Krautwald

Andreas Linkermann

Douglas R Green

Affiliations

Soon will be listed here.

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.

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