Potentiation of Fas-mediated apoptosis by attenuated production of mitochondria-derived reactive oxygen species

A. Aronis, J. Andr s. Melendez, O. Golan, S. Shilo, N. Dicter, O. Tirosh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

The role of reactive oxygen species (ROS) production in death receptor-mediated apoptosis is ill-defined. Here, we show that ROS levels play a role in moderating Fas-dependent apoptosis. Treatment of Jurkat T cells with oligomycin (ATP-synthase inhibitor) or (mitochondrial uncoupler) and Fas-activating antibody (CH11) facilitated rapid cell death that was not associated with decreased ATP production or increased DEVDase activity and cytochrome c release. However, a decrease in cellular ROS production was associated with CH11 treatment, and combinations of CH11 with oligomycin or FCCP further inhibited cellular ROS production. Thus, decreased ROS production is correlated with enhanced cell death. A transition from state 3 to state 4 mitochondrial respiration accounted for the attenuated ROS production and membrane potential. Similar observations were demonstrated in isolated rat liver mitochondria. These data show that ROS production is important in receptor-mediated apoptosis, playing a pivotal role in cell survival.

Original languageAmerican English
Pages (from-to)335-344
Number of pages10
JournalCell Death and Differentiation
Volume10
Issue number3
DOIs
StatePublished - 1 Mar 2003

Bibliographical note

Funding Information:
This research was funded by HU internal grant number 0346382 to OT and Public Health Service grant #CA77068 to JAM.

Keywords

  • Cell death
  • Mitochondria
  • Oxidants
  • Signal transduction

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