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EOH Journal Club - Fall 2017 - Antonella Marrocco

Thursday 9/28 11:00AM - 12:00PM
EOH Journal Club Seminar - Fall 2017

Date: Thursday September 28, 2017

Time: 11am - 12pm

Presenter: Antonella Marrocco

Paper: Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages

Authors: Evanna L. Mills, Beth Kelly, Angela Logan, Christian Frezza, Michael P. Murphy, Luke A. O’Neill

Abstract: 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 succinatedehydrogenase (SDH)andanelevation 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.

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Last Updated On Tuesday, September 12, 2017 by Orbell, Adam W
Created On Tuesday, September 12, 2017

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