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<title>Metabolic adaption in inflammatory macrophages through the modulation of Fe-S cluster biogenesis factors | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Metabolic adaption in inflammatory macrophages through the modulation of Fe-S cluster biogenesis factors</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session III
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">3:30 – 5:00 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NICHD</strong></p></div><div class="schedule__description"><p><strong>IMMUNO-36</strong></p></div></div></div></div><h2>Authors</h2><ul><li>WH Tong</li><li>N</li><li>Maio</li><li>D Zhang</li><li>H Wilson</li><li>M Ghosh</li><li>TA Rouault</li></ul><h2>Abstract</h2><p>Metabolic choices in immune cells are tightly linked to cell function. Inflammatory M1 macrophages undergo a shift from OXPHOS to enhanced glycolysis and pentose phosphate pathway, whereas M2 macrophages have lower glycolytic rates and higher levels of oxidative metabolism. Previous studies have shown that the metabolic switch in TLR-stimulated myeloid cells involves the activation of glycolysis through the action of AKT and HIF-1α signaling, with mitochondrial respiration decreasing mainly due to induction of inducible nitric oxide synthase (iNOS), which produces nitric oxide that damages the Fe-S cluster cofactors that are essential for mitochondrial electron transport. Our studies indicate that M1 activation also involves the active suppression of mitochondrial pyruvate catabolism through the down-regulation of the Fe-S cluster biogenesis pathway, resulting in a decrease in the activities of respiratory complexes I, succinate dehydrogenase, aconitases, and ferrochelatase, and reduced lipoylation in pyruvate dehydrogenase complex. Inhibition of glycolysis limited the TLR-stimulated repression of Fe-S cluster biogenesis factors, consistent with a vital survival function of Fe-S cluster biogenesis in cells that depend on mitochondrial ATP production, whereas activation of AMPK and inhibition of Nf-kB resulted in reduced TLR-induced suppression of Fe-S cluster biogenesis factors, indicating that the regulation of Fe-S cluster biogenesis factors are highly sensitive to cellular metabolic needs and are subject to the regulation of metabolic regulator AMPK and inflammation modulator Nf-kB. Our results suggested that repression of Fe-S cluster biogenesis/repair may serve to suppress OXPHOS and to drive metabolic and epigenetic changes needed for immune response in inflammatory macrophages.</p><p><strong>Scientific Focus Area</strong>: Immunology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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