{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:49:47Z","timestamp":1792003787785,"version":"4.4.0"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22321005"],"award-info":[{"award-number":["22321005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22361142873"],"award-info":[{"award-number":["22361142873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22525071"],"award-info":[{"award-number":["22525071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002338","name":"Ministry of Education of the People's Republic of China","doi-asserted-by":"publisher","award":["JYB2025XDXM507"],"award-info":[{"award-number":["JYB2025XDXM507"]}],"id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2022YFA1304700"],"award-info":[{"award-number":["2022YFA1304700"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021187","name":"Beijing National Laboratory for Molecular Sciences","doi-asserted-by":"publisher","award":["BNLMS-CXTD-202401"],"award-info":[{"award-number":["BNLMS-CXTD-202401"]}],"id":[{"id":"10.13039\/501100021187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The immunometabolite itaconate can covalently modify proteins through cysteine itaconation and lysine itaconylation. Current bioorthogonal itaconate probes show biased specificity for profiling cysteine itaconation in macrophages versus bacteria and are not compatible with profiling lysine itaconylation at all. Here, we report isoC3A, a universal probe designed for the comprehensive chemoproteomic profiling of these two types of itaconate-mediated modifications in both eukaryotic and prokaryotic cells. In situ profiling of Salmonella-infected macrophages by isoC3A captures the dynamic changes of itaconate-mediated modifications in the proteomes of host cells and bacteria simultaneously. It also revealed that itaconate targets critical cysteine residues on the aconitate hydratase, enhances its dehydration activity to boost the cis-aconitate level, and drives a positive feedback loop to sustain itaconate biosynthesis. Together, these findings establish isoC3A as a universal probe for exploring the covalent targets of itaconate and suggest a metabolic amplification mechanism in innate immunity.<\/jats:p>","DOI":"10.1021\/jacs.6c10764","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:01:32Z","timestamp":1790856092000},"page":"43200-43208","source":"Crossref","is-referenced-by-count":0,"title":["Cross-Species\nProfiling of Itaconate-Mediated Modifications\nby a Universal Probe"],"prefix":"10.1021","volume":"148","author":[{"given":"Bin","family":"Ma","sequence":"first","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-8563","authenticated-orcid":true,"given":"Dongyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-1268","authenticated-orcid":true,"given":"Chu","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]},{"name":"Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"8","key":"2026101414074460500_cit1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.it.2019.05.007","article-title":"The Immunomodulatory Potential of the Metabolite Itaconate","volume":"40","author":"Hooftman","year":"2019","journal-title":"Trends Immunol."},{"issue":"41","key":"2026101414074460500_cit2","doi-asserted-by":"publisher","first-page":"16386","DOI":"10.1021\/ja2070889","article-title":"Itaconic Acid Is a Mammalian Metabolite Induced during\nMacrophage Activation","volume":"133","author":"Strelko","year":"2011","journal-title":"J. Am. Chem. Soc."},{"issue":"19","key":"2026101414074460500_cit3","doi-asserted-by":"publisher","first-page":"7820","DOI":"10.1073\/pnas.1218599110","article-title":"Immune-responsive gene 1 protein\nlinks metabolism to immunity by catalyzing itaconic acid production","volume":"110","author":"Michelucci","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"7699","key":"2026101414074460500_cit4","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nature25986","article-title":"Itaconate is an anti-inflammatory metabolite that activates\nNrf2 via alkylation of KEAP1","volume":"556","author":"Mills","year":"2018","journal-title":"Nature"},{"issue":"3","key":"2026101414074460500_cit5","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.cmet.2020.07.016","article-title":"The\nImmunomodulatory Metabolite Itaconate Modifies\nNLRP3 and Inhibits Inflammasome Activation","volume":"32","author":"Hooftman","year":"2020","journal-title":"Cell Metab."},{"issue":"9","key":"2026101414074460500_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114737","article-title":"In situ chemoproteomic profiling reveals\nitaconate inhibits de novo purine biosynthesis in\npathogens","volume":"43","author":"Liu","year":"2024","journal-title":"Cell Rep."},{"issue":"15","key":"2026101414074460500_cit7","doi-asserted-by":"publisher","first-page":"2844","DOI":"10.1016\/j.molcel.2022.05.009","article-title":"Itaconate is a lysosomal inducer that promotes antibacterial\ninnate immunity","volume":"82","author":"Zhang","year":"2022","journal-title":"Mol. 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Commun."},{"issue":"7702","key":"2026101414074460500_cit10","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41586-018-0052-z","article-title":"Electrophilic properties of itaconate and derivatives\nregulate the I\u03baB\u03b6\u2013ATF3 inflammatory axis","volume":"556","author":"Bambouskova","year":"2018","journal-title":"Nature"},{"issue":"8","key":"2026101414074460500_cit11","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41418-024-01303-8","article-title":"Itaconate protects\nferroptotic neurons by alkylating GPx4 post stroke","volume":"31","author":"Wei","year":"2024","journal-title":"Cell Death Differ."},{"issue":"4","key":"2026101414074460500_cit12","doi-asserted-by":"publisher","first-page":"4729","DOI":"10.1021\/jacs.5c22156","article-title":"Dopamine-Induced Tau\nModification Prevents Pathological Phosphorylation and Generates a\nDistinct Fibril Polymorph","volume":"148","author":"Liu","year":"2026","journal-title":"J. Am. Chem. 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Chem., Int.\nEd."},{"issue":"1","key":"2026101414074460500_cit15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1039\/D2AN01370C","article-title":"A chemical probe for\nproteomic analysis and visualization of intracellular localization\nof lysine-succinylated proteins","volume":"148","author":"Umezawa","year":"2022","journal-title":"Analyst"},{"issue":"10","key":"2026101414074460500_cit16","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41589-019-0323-5","article-title":"S-glycosylation-based\ncysteine profiling reveals regulation of glycolysis by itaconate","volume":"15","author":"Qin","year":"2019","journal-title":"Nat. Chem. Biol."},{"issue":"1","key":"2026101414074460500_cit17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nmeth.2759","article-title":"A chemoproteomic\nplatform to quantitatively map targets of lipid-derived electrophiles","volume":"11","author":"Wang","year":"2014","journal-title":"Nat. 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Lett."},{"issue":"6","key":"2026101414074460500_cit24","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/nprot.2007.194","article-title":"Tandem orthogonal\nproteolysis-activity-based\nprotein profiling (TOP-ABPP)\u2500a general method for mapping sites\nof probe modification in proteomes","volume":"2","author":"Weerapana","year":"2007","journal-title":"Nat. Protoc."},{"issue":"11","key":"2026101414074460500_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110513","article-title":"Delicate regulation of IL-1\u03b2-mediated inflammation by cyclophilin\nA","volume":"38","author":"Yang","year":"2022","journal-title":"Cell Rep."},{"issue":"9","key":"2026101414074460500_cit26","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1002\/pro.5560010903","article-title":"Active site mutants of human cyclophilin\nA separate peptidyl-prolyl isomerase activity from cyclosporin A binding\nand calcineurin inhibition","volume":"1","author":"Zydowsky","year":"1992","journal-title":"Protein Sci."},{"issue":"4","key":"2026101414074460500_cit27","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.immuni.2024.03.004","article-title":"Decoding Toll-like\nreceptors: Recent insights and perspectives in innate immunity","volume":"57","author":"Kawai","year":"2024","journal-title":"Immunity"},{"issue":"3","key":"2026101414074460500_cit28","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.cell.2019.06.007","article-title":"A Bacterial Effector Reveals the\nV-ATPase-ATG16L1 Axis that Initiates Xenophagy","volume":"178","author":"Xu","year":"2019","journal-title":"Cell"},{"issue":"9","key":"2026101414074460500_cit29","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/s41564-020-0736-7","article-title":"Spatiotemporal proteomics\nuncovers cathepsin-dependent macrophage\ncell death during Salmonella infection","volume":"5","author":"Selkrig","year":"2020","journal-title":"Nat.\nMicrobiol."},{"key":"2026101414074460500_cit30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.104423","article-title":"Phosphoglycerate\nmutase regulates Treg differentiation through control of serine synthesis\nand one-carbon metabolism","volume":"14","author":"Godfrey","year":"2025","journal-title":"eLife"},{"issue":"8","key":"2026101414074460500_cit31","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1016\/j.cmet.2024.07.008","article-title":"Dopaminylation of endothelial TPI1 suppresses ferroptotic\nangiocrine signals to promote lung regeneration over fibrosis","volume":"36","author":"Mo","year":"2024","journal-title":"Cell Metab."},{"issue":"7444","key":"2026101414074460500_cit32","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate\nis an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"issue":"8011","key":"2026101414074460500_cit33","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41586-024-07254-x","article-title":"PGE2 limits\neffector expansion of\ntumour-infiltrating stem-like CD8+ T cells","volume":"629","author":"Lacher","year":"2024","journal-title":"Nature"},{"issue":"21","key":"2026101414074460500_cit34","doi-asserted-by":"publisher","first-page":"14656","DOI":"10.1074\/jbc.M113.541227","article-title":"Defective\nTibetan\nPHD2 Binding to p23 Links High Altitude Adaption to Altered Oxygen\nSensing","volume":"289","author":"Song","year":"2014","journal-title":"J. Biol. Chem."},{"issue":"43","key":"2026101414074460500_cit35","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads9181","article-title":"The chloride intracellular\nchannel\n1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation","volume":"11","author":"Rifat","year":"2025","journal-title":"Sci. Adv."},{"issue":"2","key":"2026101414074460500_cit36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032592","article-title":"Interaction\nbetween Hydrogenase Maturation\nFactors HypA and HypB Is Required for [NiFe]-Hydrogenase Maturation","volume":"7","author":"Chan","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"2026101414074460500_cit37","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1128\/JB.188.1.317-327.2006","article-title":"Comparative and Functional\nGenomic Analysis of Prokaryotic Nickel and Cobalt Uptake Transporters:\nEvidence for a Novel Group of ATP-Binding Cassette Transporters","volume":"188","author":"Rodionov","year":"2006","journal-title":"J. Bacteriol."},{"issue":"7","key":"2026101414074460500_cit38","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1021\/cr950040z","article-title":"Aconitase as Iron\u2013Sulfur\nProtein,\nEnzyme, and Iron-Regulatory Protein","volume":"96","author":"Beinert","year":"1996","journal-title":"Chem. Rev."},{"issue":"12","key":"2026101414074460500_cit39","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1110\/ps.8.12.2655","article-title":"The mechanism of\naconitase: 1.8 \u00c5 resolution crystal structure of the S642A:citrate\ncomplex","volume":"8","author":"Lloyd","year":"1999","journal-title":"Protein Sci."},{"issue":"2","key":"2026101414074460500_cit40","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41596-018-0102-x","article-title":"Ex vivo and in vivo stable isotope labelling of central\ncarbon metabolism and related pathways with analysis by LC\u2013MS\/MS","volume":"14","author":"Yuan","year":"2019","journal-title":"Nat. Protoc."}],"container-title":["Journal of the American Chemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c10764","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/40\/43200\/68724127\/jacs.6c10764.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/40\/43200\/68724127\/jacs.6c10764.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:21:53Z","timestamp":1792002113000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/40\/43200\/5443230\/Cross-Species-Profiling-of-Itaconate-Mediated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":40,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,10,1]]},"published-print":{"date-parts":[[2026,10,14]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c10764","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}