Mitochondrial ROS Production Protects the Intestine from Inflammation through Functional M2 Macrophage Polarization.

TitleMitochondrial ROS Production Protects the Intestine from Inflammation through Functional M2 Macrophage Polarization.
Publication TypeJournal Article
Year of Publication2017
AuthorsFormentini, L, Santacatterina, F, de Arenas, CNúñez, Stamatakis, K, López-Martínez, D, Logan, A, Fresno, M, Smits, R, Murphy, MP, Cuezva, JM
JournalCell Rep
Volume19
Issue6
Pagination1202-1213
Date Published2017 May 09
ISSN2211-1247
Abstract

Mitochondria are signaling hubs in cellular physiology that play a role in inflammatory diseases. We found that partial inhibition of the mitochondrial ATP synthase in the intestine of transgenic mice triggers an anti-inflammatory response through NFκB activation mediated by mitochondrial mtROS. This shielding phenotype is revealed when mice are challenged by DSS-induced colitis, which, in control animals, triggers inflammation, recruitment of M1 pro-inflammatory macrophages, and the activation of the pro-oncogenic STAT3 and Akt/mTOR pathways. In contrast, transgenic mice can polarize macrophages to the M2 anti-inflammatory phenotype. Using the mitochondria-targeted antioxidant MitoQ to quench mtROS in vivo, we observe decreased NFκB activation, preventing its cellular protective effects. These findings stress the relevance of mitochondrial signaling to the innate immune system and emphasize the potential role of the ATP synthase as a therapeutic target in inflammatory and other related diseases.

DOI10.1016/j.celrep.2017.04.036
Alternate JournalCell Rep
Citation Key10.1016/j.celrep.2017.04.036
PubMed ID28494869