ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation

Macrophage stimulation by pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide (LPS) or lipoteichoic acid (LTA) drives a proinflammatory phenotype and induces a metabolic reprogramming to sustain the cell’s function. Nevertheless, the relationship between metabolic shifts and gene...

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Autores principales:	Anna Santarsiero, Paolo Convertini, Simona Todisco, Ciro L. Pierri, Anna De Grassi, Niamh C. Williams, Dominga Iacobazzi, Giulio De Stefano, Luke A. J. O’Neill, Vittoria Infantino
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ACLY inflammation macrophages nuclear translocation NF-κB p65 acetylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4c0373f557ba404185f721458bb1f4e7
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spelling	oai:doaj.org-article:4c0373f557ba404185f721458bb1f4e72021-11-25T17:09:51ZACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation10.3390/cells101129622073-4409https://doaj.org/article/4c0373f557ba404185f721458bb1f4e72021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2962https://doaj.org/toc/2073-4409Macrophage stimulation by pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide (LPS) or lipoteichoic acid (LTA) drives a proinflammatory phenotype and induces a metabolic reprogramming to sustain the cell’s function. Nevertheless, the relationship between metabolic shifts and gene expression remains poorly explored. In this context, the metabolic enzyme ATP citrate lyase (ACLY), the producer of citrate-derived acetyl-coenzyme A (CoA), plays a critical role in supporting a proinflammatory response. Through immunocytochemistry and cytosol–nucleus fractionation, we found a short-term ACLY nuclear translocation. Protein immunoprecipitation unveiled the role of nuclear ACLY in NF-κB acetylation and in turn its full activation in human PBMC-derived macrophages. Notably, sepsis in the early hyperinflammatory phase triggers ACLY-mediated NF-κB acetylation. The ACLY/NF-κB axis increases the expression levels of proinflammatory genes, including <i>SLC25A1</i>—which encodes the mitochondrial citrate carrier—and <i>ACLY</i>, thus promoting the existence of a proinflammatory loop involving <i>SLC25A1</i> and <i>ACLY</i> genes.Anna SantarsieroPaolo ConvertiniSimona TodiscoCiro L. PierriAnna De GrassiNiamh C. WilliamsDominga IacobazziGiulio De StefanoLuke A. J. O’NeillVittoria InfantinoMDPI AGarticleACLYinflammationmacrophagesnuclear translocationNF-κBp65 acetylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2962, p 2962 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ACLY inflammation macrophages nuclear translocation NF-κB p65 acetylation Biology (General) QH301-705.5
spellingShingle	ACLY inflammation macrophages nuclear translocation NF-κB p65 acetylation Biology (General) QH301-705.5 Anna Santarsiero Paolo Convertini Simona Todisco Ciro L. Pierri Anna De Grassi Niamh C. Williams Dominga Iacobazzi Giulio De Stefano Luke A. J. O’Neill Vittoria Infantino ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
description	Macrophage stimulation by pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide (LPS) or lipoteichoic acid (LTA) drives a proinflammatory phenotype and induces a metabolic reprogramming to sustain the cell’s function. Nevertheless, the relationship between metabolic shifts and gene expression remains poorly explored. In this context, the metabolic enzyme ATP citrate lyase (ACLY), the producer of citrate-derived acetyl-coenzyme A (CoA), plays a critical role in supporting a proinflammatory response. Through immunocytochemistry and cytosol–nucleus fractionation, we found a short-term ACLY nuclear translocation. Protein immunoprecipitation unveiled the role of nuclear ACLY in NF-κB acetylation and in turn its full activation in human PBMC-derived macrophages. Notably, sepsis in the early hyperinflammatory phase triggers ACLY-mediated NF-κB acetylation. The ACLY/NF-κB axis increases the expression levels of proinflammatory genes, including <i>SLC25A1</i>—which encodes the mitochondrial citrate carrier—and <i>ACLY</i>, thus promoting the existence of a proinflammatory loop involving <i>SLC25A1</i> and <i>ACLY</i> genes.
format	article
author	Anna Santarsiero Paolo Convertini Simona Todisco Ciro L. Pierri Anna De Grassi Niamh C. Williams Dominga Iacobazzi Giulio De Stefano Luke A. J. O’Neill Vittoria Infantino
author_facet	Anna Santarsiero Paolo Convertini Simona Todisco Ciro L. Pierri Anna De Grassi Niamh C. Williams Dominga Iacobazzi Giulio De Stefano Luke A. J. O’Neill Vittoria Infantino
author_sort	Anna Santarsiero
title	ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
title_short	ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
title_full	ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
title_fullStr	ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
title_full_unstemmed	ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
title_sort	acly nuclear translocation in human macrophages drives proinflammatory gene expression by nf-κb acetylation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4c0373f557ba404185f721458bb1f4e7
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ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation

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