The mitochondrion is a major organelle contributing to energy metabolism but also a main site of ROS (reactive oxygen species) production. LPS (lipopolysaccharide)-induced ROS signalling is a critical event in macrophage activation. In the present paper we report that part of LPS-mediated ROS signalling comes from mitochondria inside a signal amplification loop that enhances MAPK (mitogen-activated protein kinase) activation. More precisely, we have identified the inner mitochondrial membrane UCP2 (uncoupling protein 2) as a physiological brake on ROS signalling. Stimulation of murine bone marrow-derived macrophages by LPS quickly down-regulated UCP2 through the JNK (c-Jun N-terminal kinase) and p38 pathways. UCP2 down-regulation was shown to be necessary to increase mitochondrial ROS production in order to potentiate MAPK activation. Consistent with this, UCP2-deficient macrophages exhibit an enhanced inflammatory state characterized by increased nitric oxide production and elevated migration ability. Additionally, we found that the absence of UCP2 renders macrophages more resistant to nitric oxide-induced apoptosis.
Skip Nav Destination
Article navigation
March 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 12 2007
Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages
Yalin Emre;
Yalin Emre
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
Search for other works by this author on:
Corinne Hurtaud;
Corinne Hurtaud
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
Search for other works by this author on:
Tobias Nübel;
Tobias Nübel
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
Search for other works by this author on:
François Criscuolo;
François Criscuolo
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
Search for other works by this author on:
Daniel Ricquier;
Daniel Ricquier
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
Search for other works by this author on:
Anne-Marie Cassard-Doulcier
Anne-Marie Cassard-Doulcier
1
1CNRS UPR 9078, Faculté de Médecine Paris 5 Descartes-Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
1To whom correspondence should be addressed (email cassard.doulcier@inserm.ipsc.u-psud.fr). Present address: Institut Paris-Sud des Cytokines, INSERM IFR13, U764, 32 rue des carnets, 92140 Clamart, France.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 19 2006
Revision Received:
October 30 2006
Accepted:
October 31 2006
Accepted Manuscript online:
October 31 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2007
Biochem J (2007) 402 (2): 271–278.
Article history
Received:
September 19 2006
Revision Received:
October 30 2006
Accepted:
October 31 2006
Accepted Manuscript online:
October 31 2006
Citation
Yalin Emre, Corinne Hurtaud, Tobias Nübel, François Criscuolo, Daniel Ricquier, Anne-Marie Cassard-Doulcier; Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages. Biochem J 1 March 2007; 402 (2): 271–278. doi: https://doi.org/10.1042/BJ20061430
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.