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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Krebs Cycle Rewired: Driver of Atherosclerosis Progression?

Author(s): Yamin Liang, Yanmei Chen, Lu Li, Shulei Zhang, Jinyan Xiao* and Dangheng Wei*

Volume 29, Issue 13, 2022

Published on: 06 August, 2021

Page: [2322 - 2333] Pages: 12

DOI: 10.2174/0929867328666210806105246

Price: $65

Abstract

The tricarboxylic acid (TCA) cycle is the center of energy metabolism in eukaryotic cells and is dynamically adjusted according to the energy needs of cells. Macrophages are activated by inflammatory stimuli, and then two breakpoints in TCA cycle lead to the accumulation of intermediates. Atherosclerosis is a chronic inflammatory process. Here, the "non-metabolic" signaling functions of TCA cycle intermediates in the macrophage under inflammatory stimulation and the role of intermediates in the progression of atherosclerosis are discussed.

Keywords: TCA cycle, citrate, succinate, itaconate, GPR91, atherosclerosis, fumarate.

« Previous Next »
[1]
Ryan, D.G.; O’Neill, L.A.J. Krebs cycle rewired for macrophage and dendritic cell effector functions. FEBS Lett., 2017, 591(19), 2992-3006.
[http://dx.doi.org/10.1002/1873-3468.12744] [PMID: 28685841]
[2]
Frostegård, J. Immunity, atherosclerosis and cardiovascular disease. BMC Med., 2013, 11, 117.
[http://dx.doi.org/10.1186/1741-7015-11-117] [PMID: 23635324]
[3]
Jinnouchi, H.; Guo, L.; Sakamoto, A.; Torii, S.; Sato, Y.; Cornelissen, A.; Kuntz, S.; Paek, K.H.; Fernandez, R.; Fuller, D.; Gadhoke, N.; Surve, D.; Romero, M.; Kolodgie, F.D.; Virmani, R.; Finn, A.V. Diversity of macrophage phenotypes and responses in atherosclerosis. Cell. Mol. Life Sci., 2020, 77(10), 1919-1932.
[http://dx.doi.org/10.1007/s00018-019-03371-3] [PMID: 31720740]
[4]
Lusis, A.J. Atherosclerosis. Nature, 2000, 407(6801), 233-241.
[http://dx.doi.org/10.1038/35025203] [PMID: 11001066]
[5]
Taleb, S. Inflammation in atherosclerosis. Arch. Cardiovasc. Dis., 2016, 109(12), 708-715.
[http://dx.doi.org/10.1016/j.acvd.2016.04.002] [PMID: 27595467]
[6]
Libby, P.; Aikawa, M.; Schönbeck, U. Cholesterol and atherosclerosis. Biochim. Biophys. Acta, 2000, 1529(1-3), 299-309.
[http://dx.doi.org/10.1016/S1388-1981(00)00161-X] [PMID: 11111097]
[7]
Yunna, C.; Mengru, H.; Lei, W.; Weidong, C. Macrophage M1/M2 polarization. Eur. J. Pharmacol., 2020, 877, 173090.
[http://dx.doi.org/10.1016/j.ejphar.2020.173090] [PMID: 32234529]
[8]
Mills, E.L.; O’Neill, L.A. Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur. J. Immunol., 2016, 46(1), 13-21.
[http://dx.doi.org/10.1002/eji.201445427] [PMID: 26643360]
[9]
Riksen, N.P.; Stienstra, R. Metabolism of innate immune cells: impact on atherosclerosis. Curr. Opin. Lipidol., 2018, 29(5), 359-367.
[http://dx.doi.org/10.1097/MOL.0000000000000539] [PMID: 30020200]
[10]
Kelly, B.; O’Neill, L.A. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res., 2015, 25(7), 771-784.
[http://dx.doi.org/10.1038/cr.2015.68] [PMID: 26045163]
[11]
Krawczyk, C.M.; Holowka, T.; Sun, J.; Blagih, J.; Amiel, E.; DeBerardinis, R.J.; Cross, J.R.; Jung, E.; Thompson, C.B.; Jones, R.G.; Pearce, E.J. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood, 2010, 115(23), 4742-4749.
[http://dx.doi.org/10.1182/blood-2009-10-249540] [PMID: 20351312]
[12]
O’Neill, L.A. A broken krebs cycle in macrophages. Immunity, 2015, 42(3), 393-394.
[http://dx.doi.org/10.1016/j.immuni.2015.02.017] [PMID: 25786167]
[13]
Jha, A.K.; Huang, S.C.; Sergushichev, A.; Lampropoulou, V.; Ivanova, Y.; Loginicheva, E.; Chmielewski, K.; Stewart, K.M.; Ashall, J.; Everts, B.; Pearce, E.J.; Driggers, E.M.; Artyomov, M.N. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity, 2015, 42(3), 419-430.
[http://dx.doi.org/10.1016/j.immuni.2015.02.005] [PMID: 25786174]
[14]
Tannahill, G.M.; Curtis, A.M.; Adamik, J.; Palsson-McDermott, E.M.; McGettrick, A.F.; Goel, G.; Frezza, C.; Bernard, N.J.; Kelly, B.; Foley, N.H.; Zheng, L.; Gardet, A.; Tong, Z.; Jany, S.S.; Corr, S.C.; Haneklaus, M.; Caffrey, B.E.; Pierce, K.; Walmsley, S.; Beasley, F.C.; Cummins, E.; Nizet, V.; Whyte, M.; Taylor, C.T.; Lin, H.; Masters, S.L.; Gottlieb, E.; Kelly, V.P.; Clish, C.; Auron, P.E.; Xavier, R.J.; O’Neill, L.A. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature, 2013, 496(7444), 238-242.
[http://dx.doi.org/10.1038/nature11986] [PMID: 23535595]
[15]
Groh, L.; Keating, S.T.; Joosten, L.A.B.; Netea, M.G.; Riksen, N.P. Monocyte and macrophage immunometabolism in atherosclerosis. Semin. Immunopathol., 2018, 40(2), 203-214.
[http://dx.doi.org/10.1007/s00281-017-0656-7] [PMID: 28971272]
[16]
Infantino, V.; Convertini, P.; Cucci, L.; Panaro, M.A.; Di Noia, M.A.; Calvello, R.; Palmieri, F.; Iacobazzi, V. The mitochondrial citrate carrier: a new player in inflammation. Biochem. J., 2011, 438(3), 433-436.
[http://dx.doi.org/10.1042/BJ20111275] [PMID: 21787310]
[17]
Roy, A.; Saqib, U.; Wary, K.; Baig, M.S. Macrophage neuronal nitric oxide synthase (NOS1) controls the inflammatory response and foam cell formation in atherosclerosis. Int. Immunopharmacol., 2020, 83, 106382.
[http://dx.doi.org/10.1016/j.intimp.2020.106382] [PMID: 32193098]
[18]
Rendra, E.; Riabov, V.; Mossel, D.M.; Sevastyanova, T.; Harmsen, M.C.; Kzhyshkowska, J. Reactive oxygen species (ROS) in macrophage activation and function in diabetes. Immunobiology, 2019, 224(2), 242-253.
[http://dx.doi.org/10.1016/j.imbio.2018.11.010] [PMID: 30739804]
[19]
Wellen, K.E.; Hatzivassiliou, G.; Sachdeva, U.M.; Bui, T.V.; Cross, J.R.; Thompson, C.B. ATP-citrate lyase links cellular metabolism to histone acetylation. Science, 2009, 324(5930), 1076-1080.
[http://dx.doi.org/10.1126/science.1164097] [PMID: 19461003]
[20]
Infantino, V.; Iacobazzi, V.; Palmieri, F.; Menga, A. ATP-citrate lyase is essential for macrophage inflammatory response. Biochem. Biophys. Res. Commun., 2013, 440(1), 105-111.
[http://dx.doi.org/10.1016/j.bbrc.2013.09.037] [PMID: 24051091]
[21]
Feng, X.; Zhang, L.; Xu, S.; Shen, A.Z. ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: An updated review. Prog. Lipid Res., 2020, 77, 101006.
[http://dx.doi.org/10.1016/j.plipres.2019.101006] [PMID: 31499095]
[22]
Infantino, V.; Iacobazzi, V.; Menga, A.; Avantaggiati, M.L.; 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.
[http://dx.doi.org/10.1016/j.bbagrm.2014.07.013] [PMID: 25072865]
[23]
Shen, Y.; Wei, W.; Zhou, D.X. Histone acetylation enzymes coordinate metabolism and gene expression. Trends Plant Sci., 2015, 20(10), 614-621.
[http://dx.doi.org/10.1016/j.tplants.2015.07.005] [PMID: 26440431]
[24]
Trefely, S.; Doan, M.T.; Snyder, N.W. Crosstalk between cellular metabolism and histone acetylation. Methods Enzymol., 2019, 626, 1-21.
[http://dx.doi.org/10.1016/bs.mie.2019.07.013] [PMID: 31606071]
[25]
Daskalaki, M.G.; Tsatsanis, C.; Kampranis, S.C. Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J. Cell. Physiol., 2018, 233(9), 6495-6507.
[http://dx.doi.org/10.1002/jcp.26497] [PMID: 29574768]
[26]
Iacobazzi, V.; Infantino, V. Citrate--new functions for an old metabolite. Biol. Chem., 2014, 395(4), 387-399.
[http://dx.doi.org/10.1515/hsz-2013-0271] [PMID: 24445237]
[27]
Ference, B.A.; Ginsberg, H.N.; Graham, I.; Ray, K.K.; Packard, C.J.; Bruckert, E.; Hegele, R.A.; Krauss, R.M.; Raal, F.J.; Schunkert, H.; Watts, G.F.; Borén, J.; Fazio, S.; Horton, J.D.; Masana, L.; Nicholls, S.J.; Nordestgaard, B.G.; van de Sluis, B.; Taskinen, M.R.; Tokgözoglu, L.; Landmesser, U.; Laufs, U.; Wiklund, O.; Stock, J.K.; Chapman, M.J.; Catapano, A.L. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J., 2017, 38(32), 2459-2472.
[http://dx.doi.org/10.1093/eurheartj/ehx144] [PMID: 28444290]
[28]
Molusky, M.M.; Hsieh, J.; Lee, S.X.; Ramakrishnan, R.; Tascau, L.; Haeusler, R.A.; Accili, D.; Tall, A.R. Metformin and AMP kinase activation increase expression of the sterol transporters ABCG5/8 (ATP-binding cassette transporter G5/G8) with potential antiatherogenic consequences. Arterioscler. Thromb. Vasc. Biol., 2018, 38(7), 1493-1503.
[http://dx.doi.org/10.1161/ATVBAHA.118.311212] [PMID: 29853564]
[29]
Nikolic, D.; Mikhailidis, D.P.; Davidson, M.H.; Rizzo, M.; Banach, M. ETC-1002: a future option for lipid disorders? Atherosclerosis, 2014, 237(2), 705-710.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.10.099] [PMID: 25463109]
[30]
Burke, A.C.; Telford, D.E.; Huff, M.W. Bempedoic acid: effects on lipoprotein metabolism and atherosclerosis. Curr. Opin. Lipidol., 2019, 30(1), 1-9.
[http://dx.doi.org/10.1097/MOL.0000000000000565] [PMID: 30586346]
[31]
Zagelbaum, N.K.; Yandrapalli, S.; Nabors, C.; Frishman, W.H. Bempedoic Acid (ETC-1002): ATP Citrate Lyase Inhibitor: Review of a First-in-Class Medication with Potential Benefit in Statin-Refractory Cases. Cardiol. Rev., 2019, 27(1), 49-56.
[http://dx.doi.org/10.1097/CRD.0000000000000218] [PMID: 29939848]
[32]
Ryan, D.G.; Murphy, M.P.; Frezza, C.; Prag, H.A.; Chouchani, E.T.; O’Neill, L.A.; Mills, E.L. Coupling Krebs cycle metabolites to signalling in immunity and cancer. Nat. Metab., 2019, 1, 16-33.
[http://dx.doi.org/10.1038/s42255-018-0014-7] [PMID: 31032474]
[33]
Yu, X.H.; Zhang, D.W.; Zheng, X.L.; Tang, C.K. Itaconate: an emerging determinant of inflammation in activated macrophages. Immunol. Cell Biol., 2019, 97(2), 134-141.
[PMID: 30428148]
[34]
Lampropoulou, V.; Sergushichev, A.; Bambouskova, M.; Nair, S.; Vincent, E.E.; Loginicheva, E.; Cervantes-Barragan, L.; Ma, X.; Huang, S.C.; Griss, T.; Weinheimer, C.J.; Khader, S.; Randolph, G.J.; Pearce, E.J.; Jones, R.G.; Diwan, A.; Diamond, M.S.; Artyomov, M.N. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab., 2016, 24(1), 158-166.
[http://dx.doi.org/10.1016/j.cmet.2016.06.004] [PMID: 27374498]
[35]
Bambouskova, M.; Gorvel, L.; Lampropoulou, V.; Sergushichev, A.; Loginicheva, E.; Johnson, K.; Korenfeld, D.; Mathyer, M.E.; Kim, H.; Huang, L.H.; Duncan, D.; Bregman, H.; Keskin, A.; Santeford, A.; Apte, R.S.; Sehgal, R.; Johnson, B.; Amarasinghe, G.K.; Soares, M.P.; Satoh, T.; Akira, S.; Hai, T.; de Guzman Strong, C.; Auclair, K.; Roddy, T.P.; Biller, S.A.; Jovanovic, M.; Klechevsky, E.; Stewart, K.M.; Randolph, G.J.; Artyomov, M.N. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature, 2018, 556(7702), 501-504.
[http://dx.doi.org/10.1038/s41586-018-0052-z] [PMID: 29670287]
[36]
Mills, E.L.; Ryan, D.G.; Prag, H.A.; Dikovskaya, D.; Menon, D.; Zaslona, Z.; Jedrychowski, M.P.; Costa, A.S.H.; Higgins, M.; Hams, E.; Szpyt, J.; Runtsch, M.C.; King, M.S.; McGouran, J.F.; Fischer, R.; Kessler, B.M.; McGettrick, A.F.; Hughes, M.M.; Carroll, R.G.; Booty, L.M.; Knatko, E.V.; Meakin, P.J.; Ashford, M.L.J.; Modis, L.K.; Brunori, G.; Sévin, D.C.; Fallon, P.G.; Caldwell, S.T.; Kunji, E.R.S.; Chouchani, E.T.; Frezza, C.; Dinkova-Kostova, A.T.; Hartley, R.C.; Murphy, M.P.; O’Neill, L.A. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature, 2018, 556(7699), 113-117.
[http://dx.doi.org/10.1038/nature25986] [PMID: 29590092]
[37]
Nair, S.; Huynh, J.P.; Lampropoulou, V.; Loginicheva, E.; Esaulova, E.; Gounder, A.P.; Boon, A.C.M.; Schwarzkopf, E.A.; Bradstreet, T.R.; Edelson, B.T.; Artyomov, M.N.; Stallings, C.L.; Diamond, M.S. Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection. J. Exp. Med., 2018, 215(4), 1035-1045.
[http://dx.doi.org/10.1084/jem.20180118] [PMID: 29511063]
[38]
O’Neill, L.A.J.; Artyomov, M.N. Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat. Rev. Immunol., 2019, 19(5), 273-281.
[http://dx.doi.org/10.1038/s41577-019-0128-5] [PMID: 30705422]
[39]
Cordes, T.; Wallace, M.; Michelucci, A.; Divakaruni, A.S.; Sapcariu, S.C.; Sousa, C.; Koseki, H.; Cabrales, P.; Murphy, A.N.; Hiller, K.; Metallo, C.M. Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels. J. Biol. Chem., 2016, 291(27), 14274-14284.
[http://dx.doi.org/10.1074/jbc.M115.685792] [PMID: 27189937]
[40]
Németh, B.; Doczi, J.; Csete, D.; Kacso, G.; Ravasz, D.; Adams, D.; Kiss, G.; Nagy, A.M.; Horvath, G.; Tretter, L.; Mócsai, A.; Csépányi-Kömi, R.; Iordanov, I.; Adam-Vizi, V.; Chinopoulos, C. Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage. FASEB J., 2016, 30(1), 286-300.
[http://dx.doi.org/10.1096/fj.15-279398] [PMID: 26358042]
[41]
Mills, E.; O’Neill, L.A. Succinate: a metabolic signal in inflammation. Trends Cell Biol., 2014, 24(5), 313-320.
[http://dx.doi.org/10.1016/j.tcb.2013.11.008] [PMID: 24361092]
[42]
He, W.; Miao, F.J.; Lin, D.C.; Schwandner, R.T.; Wang, Z.; Gao, J.; Chen, J.L.; Tian, H.; Ling, L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature, 2004, 429(6988), 188-193.
[http://dx.doi.org/10.1038/nature02488] [PMID: 15141213]
[43]
Littlewood-Evans, A.; Sarret, S.; Apfel, V.; Loesle, P.; Dawson, J.; Zhang, J.; Muller, A.; Tigani, B.; Kneuer, R.; Patel, S.; Valeaux, S.; Gommermann, N.; Rubic-Schneider, T.; Junt, T.; Carballido, J.M. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis. J. Exp. Med., 2016, 213(9), 1655-1662.
[http://dx.doi.org/10.1084/jem.20160061] [PMID: 27481132]
[44]
Rubic, T.; Lametschwandtner, G.; Jost, S.; Hinteregger, S.; Kund, J.; Carballido-Perrig, N.; Schwärzler, C.; Junt, T.; Voshol, H.; Meingassner, J.G.; Mao, X.; Werner, G.; Rot, A.; Carballido, J.M. Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat. Immunol., 2008, 9(11), 1261-1269.
[http://dx.doi.org/10.1038/ni.1657] [PMID: 18820681]
[45]
Ariza, A.C.; Deen, P.M.; Robben, J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions. Front. Endocrinol. (Lausanne), 2012, 3, 22.
[http://dx.doi.org/10.3389/fendo.2012.00022] [PMID: 22649411]
[46]
Guzy, R.D.; Sharma, B.; Bell, E.; Chandel, N.S.; Schumacker, P.T. Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol. Cell. Biol., 2008, 28(2), 718-731.
[http://dx.doi.org/10.1128/MCB.01338-07] [PMID: 17967865]
[47]
Kietzmann, T.; Görlach, A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin. Cell Dev. Biol., 2005, 16(4-5), 474-486.
[http://dx.doi.org/10.1016/j.semcdb.2005.03.010] [PMID: 15905109]
[48]
Mills, E.L.; Kelly, B.; Logan, A.; Costa, A.S.H.; Varma, M.; Bryant, C.E.; Tourlomousis, P.; Däbritz, J.H.M.; Gottlieb, E.; Latorre, I.; Corr, S.C.; McManus, G.; Ryan, D.; Jacobs, H.T.; Szibor, M.; Xavier, R.J.; Braun, T.; Frezza, C.; Murphy, M.P.; O’Neill, L.A. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell, 2016, 167(2), 457-470.e13.
[http://dx.doi.org/10.1016/j.cell.2016.08.064] [PMID: 27667687]
[49]
Chouchani, E.T.; Pell, V.R.; Gaude, E.; Aksentijević, D.; Sundier, S.Y.; Robb, E.L.; Logan, A.; Nadtochiy, S.M.; Ord, E.N.J.; Smith, A.C.; Eyassu, F.; Shirley, R.; Hu, C.H.; Dare, A.J.; James, A.M.; Rogatti, S.; Hartley, R.C.; Eaton, S.; Costa, A.S.H.; Brookes, P.S.; Davidson, S.M.; Duchen, M.R.; Saeb-Parsy, K.; Shattock, M.J.; Robinson, A.J.; Work, L.M.; Frezza, C.; Krieg, T.; Murphy, M.P. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature, 2014, 515(7527), 431-435.
[http://dx.doi.org/10.1038/nature13909] [PMID: 25383517]
[50]
Xiao, M.; Yang, H.; Xu, W.; Ma, S.; Lin, H.; Zhu, H.; Liu, L.; Liu, Y.; Yang, C.; Xu, Y.; Zhao, S.; Ye, D.; Xiong, Y.; Guan, K.L. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev., 2012, 26(12), 1326-1338.
[http://dx.doi.org/10.1101/gad.191056.112] [PMID: 22677546]
[51]
Bénit, P.; Letouzé, E.; Rak, M.; Aubry, L.; Burnichon, N.; Favier, J.; Gimenez-Roqueplo, A.P.; Rustin, P. Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling. Biochim. Biophys. Acta, 2014, 1837(8), 1330-1337.
[http://dx.doi.org/10.1016/j.bbabio.2014.03.013] [PMID: 24699309]
[52]
Brigati, C.; Banelli, B.; di Vinci, A.; Casciano, I.; Allemanni, G.; Forlani, A.; Borzì, L.; Romani, M. Inflammation, HIF-1, and the epigenetics that follows. Mediators Inflamm., 2010, 2010, 263914.
[http://dx.doi.org/10.1155/2010/263914] [PMID: 21197398]
[53]
Selak, M.A.; Armour, S.M.; MacKenzie, E.D.; Boulahbel, H.; Watson, D.G.; Mansfield, K.D.; Pan, Y.; Simon, M.C.; Thompson, C.B.; Gottlieb, E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell, 2005, 7(1), 77-85.
[http://dx.doi.org/10.1016/j.ccr.2004.11.022] [PMID: 15652751]
[54]
Brière, J.J.; Favier, J.; Bénit, P.; El Ghouzzi, V.; Lorenzato, A.; Rabier, D.; Di Renzo, M.F.; Gimenez-Roqueplo, A.P.; Rustin, P. Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions. Hum. Mol. Genet., 2005, 14(21), 3263-3269.
[http://dx.doi.org/10.1093/hmg/ddi359] [PMID: 16195397]
[55]
Murphy, M.P. How mitochondria produce reactive oxygen species. Biochem. J., 2009, 417(1), 1-13.
[http://dx.doi.org/10.1042/BJ20081386] [PMID: 19061483]
[56]
Feng, S.; Jiao, K.; Guo, H.; Jiang, M.; Hao, J.; Wang, H.; Shen, C. Succinyl-proteome profiling of Dendrobium officinale, an important traditional Chinese orchid herb, revealed involvement of succinylation in the glycolysis pathway. BMC Genomics, 2017, 18(1), 598.
[http://dx.doi.org/10.1186/s12864-017-3978-x] [PMID: 28797234]
[57]
Gibson, G.E.; Xu, H.; Chen, H.L.; Chen, W.; Denton, T.T.; Zhang, S. Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines. J. Neurochem., 2015, 134(1), 86-96.
[http://dx.doi.org/10.1111/jnc.13096] [PMID: 25772995]
[58]
Du, J.; Zhou, Y.; Su, X.; Yu, J.J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Kim, J.H.; Choi, B.H.; He, B.; Chen, W.; Zhang, S.; Cerione, R.A.; Auwerx, J.; Hao, Q.; Lin, H. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science, 2011, 334(6057), 806-809.
[http://dx.doi.org/10.1126/science.1207861] [PMID: 22076378]
[59]
Wang, F.; Wang, K.; Xu, W.; Zhao, S.; Ye, D.; Wang, Y.; Xu, Y.; Zhou, L.; Chu, Y.; Zhang, C.; Qin, X.; Yang, P.; Yu, H. SIRT5 Desuccinylates and Activates Pyruvate Kinase M2 to Block Macrophage IL-1β Production and to Prevent DSS-Induced Colitis in Mice. Cell Rep., 2017, 19(11), 2331-2344.
[http://dx.doi.org/10.1016/j.celrep.2017.05.065] [PMID: 28614718]
[60]
Frezza, C. Mitochondrial metabolites: undercover signalling molecules. Interface Focus, 2017, 7(2), 20160100.
[http://dx.doi.org/10.1098/rsfs.2016.0100] [PMID: 28382199]
[61]
Cheng, S.C.; Quintin, J.; Cramer, R.A.; Shepardson, K.M.; Saeed, S.; Kumar, V.; Giamarellos-Bourboulis, E.J.; Martens, J.H.; Rao, N.A.; Aghajanirefah, A.; Manjeri, G.R.; Li, Y.; Ifrim, D.C.; Arts, R.J.; van der Veer, B.M.; Deen, P.M.; Logie, C.; O’Neill, L.A.; Willems, P.; van de Veerdonk, F.L.; van der Meer, J.W.; Ng, A.; Joosten, L.A.; Wijmenga, C.; Stunnenberg, H.G.; Xavier, R.J.; Netea, M.G. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 2014, 345(6204), 1250684.
[http://dx.doi.org/10.1126/science.1250684] [PMID: 25258083]
[62]
Arts, R.J.; Novakovic, B.; Ter Horst, R.; Carvalho, A.; Bekkering, S.; Lachmandas, E.; Rodrigues, F.; Silvestre, R.; Cheng, S.C.; Wang, S.Y.; Habibi, E.; Gonçalves, L.G.; Mesquita, I.; Cunha, C.; van Laarhoven, A.; van de Veerdonk, F.L.; Williams, D.L.; van der Meer, J.W.; Logie, C.; O’Neill, L.A.; Dinarello, C.A.; Riksen, N.P.; van Crevel, R.; Clish, C.; Notebaart, R.A.; Joosten, L.A.; Stunnenberg, H.G.; Xavier, R.J.; Netea, M.G. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab., 2016, 24(6), 807-819.
[http://dx.doi.org/10.1016/j.cmet.2016.10.008] [PMID: 27866838]
[63]
Mills, E.L.; Kelly, B.; O’Neill, L.A.J. Mitochondria are the powerhouses of immunity. Nat. Immunol., 2017, 18(5), 488-498.
[http://dx.doi.org/10.1038/ni.3704] [PMID: 28418387]
[64]
Riksen, N.P.; Netea, M.G. Immunometabolic control of trained immunity. Mol. Aspects Med., 2021, 77, 100897.
[http://dx.doi.org/10.1016/j.mam.2020.100897] [PMID: 32891423]
[65]
Kobayashi, E.H.; Suzuki, T.; Funayama, R.; Nagashima, T.; Hayashi, M.; Sekine, H.; Tanaka, N.; Moriguchi, T.; Motohashi, H.; Nakayama, K.; Yamamoto, M. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun., 2016, 7, 11624.
[http://dx.doi.org/10.1038/ncomms11624] [PMID: 27211851]
[66]
Ashrafian, H.; Czibik, G.; Bellahcene, M.; Aksentijević, D.; Smith, A.C.; Mitchell, S.J.; Dodd, M.S.; Kirwan, J.; Byrne, J.J.; Ludwig, C.; Isackson, H.; Yavari, A.; Støttrup, N.B.; Contractor, H.; Cahill, T.J.; Sahgal, N.; Ball, D.R.; Birkler, R.I.; Hargreaves, I.; Tennant, D.A.; Land, J.; Lygate, C.A.; Johannsen, M.; Kharbanda, R.K.; Neubauer, S.; Redwood, C.; de Cabo, R.; Ahmet, I.; Talan, M.; Günther, U.L.; Robinson, A.J.; Viant, M. [R.; Pollard, P.J.; Tyler, D.J.; Watkins, H. Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway. Cell Metab., 2012, 15(3), 361-371.
[http://dx.doi.org/10.1016/j.cmet.2012.01.017] [PMID: 22405071]
[67]
Sciacovelli, M.; Gonçalves, E.; Johnson, T.I.; Zecchini, V.R.; da Costa, A.S.; Gaude, E.; Drubbel, A.V.; Theobald, S.J.; Abbo, S.R.; Tran, M.G.; Rajeeve, V.; Cardaci, S.; Foster, S.; Yun, H.; Cutillas, P.; Warren, A.; Gnanapragasam, V.; Gottlieb, E.; Franze, K.; Huntly, B.; Maher, E.R.; Maxwell, P.H.; Saez-Rodriguez, J.; Frezza, C. Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature, 2016, 537(7621), 544-547.
[http://dx.doi.org/10.1038/nature19353] [PMID: 27580029]
[68]
Liu, R.; Chen, L.; Wang, Y.; Zhang, G.; Cheng, Y.; Feng, Z.; Bai, X.; Liu, J. High ratio of ω-3/ω-6 polyunsaturated fatty acids targets mTORC1 to prevent high-fat diet-induced metabolic syndrome and mitochondrial dysfunction in mice. J. Nutr. Biochem., 2020, 79, 108330.
[http://dx.doi.org/10.1016/j.jnutbio.2019.108330] [PMID: 32179408]
[69]
Tomas, L.; Edsfeldt, A.; Mollet, I.G.; Perisic Matic, L.; Prehn, C.; Adamski, J.; Paulsson-Berne, G.; Hedin, U.; Nilsson, J.; Bengtsson, E.; Gonçalves, I.; Björkbacka, H. Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques. Eur. Heart J., 2018, 39(24), 2301-2310.
[http://dx.doi.org/10.1093/eurheartj/ehy124] [PMID: 29562241]
[70]
Yamashita, A.; Zhao, Y.; Matsuura, Y.; Yamasaki, K.; Moriguchi-Goto, S.; Sugita, C.; Iwakiri, T.; Okuyama, N.; Koshimoto, C.; Kawai, K.; Tamaki, N.; Zhao, S.; Kuge, Y.; Asada, Y. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage. PLoS One, 2014, 9(1), e86426.
[http://dx.doi.org/10.1371/journal.pone.0086426] [PMID: 24466087]
[71]
Matsui, R.; Xu, S.; Maitland, K.A.; Mastroianni, R.; Leopold, J.A.; Handy, D.E.; Loscalzo, J.; Cohen, R.A. Glucose-6-phosphate dehydrogenase deficiency decreases vascular superoxide and atherosclerotic lesions in apolipoprotein E(-/-) mice. Arterioscler. Thromb. Vasc. Biol., 2006, 26(4), 910-916.
[http://dx.doi.org/10.1161/01.ATV.0000205850.49390.3b] [PMID: 16439706]
[72]
Baardman, J.; Verberk, S.G.S.; Prange, K.H.M.; van Weeghel, M.; van der Velden, S.; Ryan, D.G.; Wüst, R.C.I.; Neele, A.E.; Speijer, D.; Denis, S.W.; Witte, M.E.; Houtkooper, R.H.; O’neill, L.A.; Knatko, E.V.; Dinkova-Kostova, A.T.; Lutgens, E.; de Winther, M.P.J.; Van den Bossche, J. A defective pentose phosphate pathway reduces inflammatory macrophage responses during hypercholesterolemia. Cell Rep., 2018, 25(8), 2044-2052.e5.
[http://dx.doi.org/10.1016/j.celrep.2018.10.092] [PMID: 30463003]
[73]
Patil, N.K.; Bohannon, J.K.; Hernandez, A.; Patil, T.K.; Sherwood, E.R. Regulation of leukocyte function by citric acid cycle intermediates. J. Leukoc. Biol., 2019, 106(1), 105-117.
[http://dx.doi.org/10.1002/JLB.3MIR1118-415R] [PMID: 30791134]
[74]
Valls-Lacalle, L.; Barba, I.; Miró-Casas, E.; Alburquerque-Béjar, J.J.; Ruiz-Meana, M.; Fuertes-Agudo, M.; Rodríguez-Sinovas, A.; García-Dorado, D. Succinate dehydrogenase inhibition with malonate during reperfusion reduces infarct size by preventing mitochondrial permeability transition. Cardiovasc. Res., 2016, 109(3), 374-384.
[http://dx.doi.org/10.1093/cvr/cvv279] [PMID: 26705364]
[75]
Murphy, M.P.; O’Neill, L.A.J. Krebs cycle reimagined: the emerging roles of succinate and itaconate as signal transducers. Cell, 2018, 174(4), 780-784.
[http://dx.doi.org/10.1016/j.cell.2018.07.030] [PMID: 30096309]

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