Metabolism and Acetylation in Innate Immune Cell Function and Fate

Overview

Journal Semin Immunol

Specialty Allergy & Immunology

Date 2017 Mar 26

PMID 28340958

Citations 27

Authors

Alanna M Cameron

Simon J Lawless

Edward J Pearce

Affiliations

Soon will be listed here.

Abstract

Innate immunity is the first line of defense against invading pathogens. Changes in both metabolism and chromatin accessibility contribute to the shaping of these innate immune responses, and we are beginning to appreciate that cross-talk between these two systems plays an important role in determining innate immune cell differentiation and function. In this review we focus on acetylation, a post-translational modification important for both regulating chromatin accessibility by modulating histone function, and for functional regulation of non-histone proteins, which has many links to both immune signaling and metabolism. We discuss the interactions between metabolism and acetylation, including the requirement for metabolic intermediates as substrates and co-factors for acetylation, and the regulation of metabolic proteins and enzymes by acetylation. Here we highlight recent findings, which demonstrate the role that the metabolism-acetylation axis has in coordinating the responses of innate immune cells to the availability of nutrients and the microenvironment.

Citing Articles

Adipose stem cells regulate lipid metabolism by upregulating mitochondrial fatty acid β-oxidation in macrophages to improve the retention rate of transplanted fat.

Li J, Guo T, Li Y, Wang Q, Du Y, Li R Stem Cell Res Ther. 2024; 15(1):328.

PMID: 39334483 PMC: 11438425. DOI: 10.1186/s13287-024-03953-4.

H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome.

Gupta P, Barak S, Feuermann Y, Goobes G, Kaphzan H Mol Autism. 2024; 15(1):31.

PMID: 39049050 PMC: 11267930. DOI: 10.1186/s13229-024-00608-2.

Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration.

Huang L, Chen X, Yang X, Zhang Y, Liang Y, Qiu X Front Cell Dev Biol. 2024; 12:1394582.

PMID: 38863943 PMC: 11165363. DOI: 10.3389/fcell.2024.1394582.

Defining the metabolic signatures associated with human macrophage polarisation.

Povo-Retana A, Landauro-Vera R, Farinas M, Sanchez-Garcia S, Alvarez-Lucena C, Marin S Biochem Soc Trans. 2023; 51(4):1429-1436.

PMID: 37449892 PMC: 10586766. DOI: 10.1042/BST20220504.

Itaconate family-based host-directed therapeutics for infections.

Yuk J, Park E, Kim I, Jo E Front Immunol. 2023; 14:1203756.

PMID: 37261340 PMC: 10228716. DOI: 10.3389/fimmu.2023.1203756.

References

Park C, Rehrauer H, Mansuy I . Genome-wide analysis of H4K5 acetylation associated with fear memory in mice. BMC Genomics. 2013; 14:539. PMC: 3751108. DOI: 10.1186/1471-2164-14-539. View

Lu L, Chen X, Sanders D, Qian S, Zhong X . High-resolution mapping of H4K16 and H3K23 acetylation reveals conserved and unique distribution patterns in Arabidopsis and rice. Epigenetics. 2015; 10(11):1044-53. PMC: 4844217. DOI: 10.1080/15592294.2015.1104446. View

Palmieri E, Spera I, Menga A, Infantino V, Porcelli V, Iacobazzi V . Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation. Biochim Biophys Acta. 2015; 1847(8):729-38. DOI: 10.1016/j.bbabio.2015.04.009. View

Taylor G, Eskeland R, Hekimoglu-Balkan B, Pradeepa M, Bickmore W . H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res. 2013; 23(12):2053-65. PMC: 3847775. DOI: 10.1101/gr.155028.113. View

Rodgers J, Lerin C, Haas W, Gygi S, Spiegelman B, Puigserver P . Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434(7029):113-8. DOI: 10.1038/nature03354. View

Zhang R, Chen H, Liu J, Jia Y, Zhang Z, Yang R . SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages. J Biol Chem. 2010; 285(10):7097-110. PMC: 2844159. DOI: 10.1074/jbc.M109.038604. View

Smith K, Workman J . Introducing the acetylome. Nat Biotechnol. 2009; 27(10):917-9. DOI: 10.1038/nbt1009-917. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Newman J, Verdin E . β-hydroxybutyrate: much more than a metabolite. Diabetes Res Clin Pract. 2014; 106(2):173-81. PMC: 4414487. DOI: 10.1016/j.diabres.2014.08.009. View

10.

Mullican S, Gaddis C, Alenghat T, Nair M, Giacomin P, Everett L . Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev. 2011; 25(23):2480-8. PMC: 3243058. DOI: 10.1101/gad.175950.111. View

11.

Guo R, Chen J, Mitchell D, Johnson D . GCN5 and E2F1 stimulate nucleotide excision repair by promoting H3K9 acetylation at sites of damage. Nucleic Acids Res. 2010; 39(4):1390-7. PMC: 3045616. DOI: 10.1093/nar/gkq983. View

12.

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

13.

Barber M, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z . SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012; 487(7405):114-8. PMC: 3412143. DOI: 10.1038/nature11043. View

14.

Covarrubias A, Aksoylar H, Yu J, Snyder N, Worth A, Iyer S . Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. Elife. 2016; 5. PMC: 4769166. DOI: 10.7554/eLife.11612. View

15.

Prokesch A, Pelzmann H, Pessentheiner A, Huber K, Madreiter-Sokolowski C, Drougard A . N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes. Sci Rep. 2016; 6:23723. PMC: 4820693. DOI: 10.1038/srep23723. View

16.

Jenuwein T, Allis C . Translating the histone code. Science. 2001; 293(5532):1074-80. DOI: 10.1126/science.1063127. View

17.

Jha A, Huang S, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E . Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015; 42(3):419-30. DOI: 10.1016/j.immuni.2015.02.005. View

18.

Shimazu T, Hirschey M, Newman J, He W, Shirakawa K, Le Moan N . Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2012; 339(6116):211-4. PMC: 3735349. DOI: 10.1126/science.1227166. View

19.

Infantino V, Iacobazzi V, Menga A, Avantaggiati M, Palmieri F . A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation. Biochim Biophys Acta. 2014; 1839(11):1217-1225. PMC: 4346166. DOI: 10.1016/j.bbagrm.2014.07.013. View

20.

Alvarez Y, Rodriguez M, Municio C, Hugo E, Alonso S, Ibarrola N . Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells. J Biol Chem. 2012; 287(42):35689-35701. PMC: 3471763. DOI: 10.1074/jbc.M112.391839. View