GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway

Menon, Deepthi, Coll, Rebecca, O'Neill, Luke A. J and Board, Philip G (2015) GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway. Journal of Cell Science, 128 10: 1982-1990. doi:10.1242/jcs.167858

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ363000_OA.pdf Full text (open access) application/pdf 1.03MB 0

Author Menon, Deepthi
Coll, Rebecca
O'Neill, Luke A. J
Board, Philip G
Title GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
Publication date 2015-05-15
Year available 2015
Sub-type Article (original research)
DOI 10.1242/jcs.167858
Open Access Status File (Publisher version)
Volume 128
Issue 10
Start page 1982
End page 1990
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Abstract Macrophages mediate innate immune responses that recognise foreign pathogens, and bacterial lipopolysaccharide (LPS) recruits a signalling pathway through Toll-like receptor 4 (TLR4) to induce pro-inflammatory cytokines and reactive oxygen species (ROS). LPS activation also skews the metabolism of macrophages towards a glycolytic phenotype. Here, we demonstrate that the LPS-triggered glycolytic switch is significantly attenuated in macrophages deficient for glutathione transferase omega-1 (GSTO1, note that GSTO1-1 refers to the dimeric molecule with identical type 1 subunits). In response to LPS, GSTO1-1-deficient macrophages do not produce excess lactate, or dephosphorylate AMPK, a key metabolic stress regulator. In addition, GSTO1-1-deficient cells do not induce HIF1α, which plays a key role in maintaining the pro-inflammatory state of activated macrophages. The accumulation of the TCA cycle intermediates succinate and fumarate that occurs in LPS-treated macrophages was also blocked in GSTO1-1-deficient cells. These data indicate that GSTO1-1 is required for LPS-mediated signalling in macrophages and that it acts early in the LPS–TLR4 pro-inflammatory pathway.
Keyword Metabolism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 14 Jun 2015, 10:34:04 EST by System User on behalf of Scholarly Communication and Digitisation Service