E-resources
-
Mills, Evanna L.; Kelly, Beth; Logan, Angela; Costa, Ana S.H.; Varma, Mukund; Bryant, Clare E.; Tourlomousis, Panagiotis; Däbritz, J. Henry M.; Gottlieb, Eyal; Latorre, Isabel; Corr, Sinéad C.; McManus, Gavin; Ryan, Dylan; Jacobs, Howard T.; Szibor, Marten; Xavier, Ramnik J.; Braun, Thomas; Frezza, Christian; Murphy, Michael P.; O’Neill, Luke A.
Cell, 10/2016, Volume: 167, Issue: 2Journal Article
Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state. Display omitted •LPS induces mitochondrial repurposing from ATP synthesis to ROS production•Oxidation of succinate and mitochondrial hyperpolarization drive ROS production•Blocking LPS-induced ROS production or hyperpolarization inhibits IL-1β•SDH is critical for the inflammatory response To support their pro-inflammatory function, activated macrophages repurpose their mitochondria, switching from ATP production to ROS generation.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.