alexa Link between mitochondria and NADPH oxidase 1 isozyme for the sustained production of reactive oxygen species and cell death.


Journal of Cell Signaling

Author(s): Lee SB, Bae IH, Bae YS, Um HD

Abstract Share this page

Abstract Although mitochondria and the Nox family of NADPH oxidase are major sources of reactive oxygen species (ROS) induced by external stimuli, there is limited information on their functional relationship. This study has shown that serum withdrawal promotes the production of ROS in human 293T cells by stimulating both the mitochondria and Nox1. An analysis of their relationship revealed that the mitochondria respond to serum withdrawal within a few minutes, and the ROS produced by the mitochondria trigger Nox1 action by stimulating phosphoinositide 3-kinase (PI3K) and Rac1. Activation of the PI3K/Rac1/Nox1 pathway was evident 4-8 h after but not earlier than serum withdrawal initiation, and this time lag was found to be required for an additional activator of the pathway, Lyn, to be expressed. Functional analysis suggested that, although the mitochondria contribute to the early (0-4 h) accumulation of ROS, the maintenance of the induced ROS levels to the later (4-8 h) phase required the action of the PI3K/Rac1/Nox1 pathway. Serum withdrawal-treated cells eventually lost their viability, which was reversed by blocking either the mitochondria-dependent induction of ROS using rotenone or KCN or the PI3K/Rac1/Nox1 pathway using the dominant negative mutants or small interfering RNAs. This suggests that mitochondrial ROS are essential but not enough to promote cell death, which requires the sustained accumulation of ROS by the subsequent action of Nox1. Overall, this study shows a signaling link between the mitochondria and Nox1, which is crucial for the sustained accumulation of ROS and cell death in serum withdrawal-induced signaling. This article was published in J Biol Chem and referenced in Journal of Cell Signaling

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version