⮝ Full datasets listing
PXD063862
PXD063862 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | SIRT4 Controls Macrophage Function and Wound Healing through Control of Protein Itaconylation in Mice |
| Description | Proper regulation of inflammatory responses is essential for organismal health. Dysregulation can lead to accelerated development of the diseases of aging and the aging process itself. Here, we identify a novel enzymatic activity of the mitochondrial sirtuin SIRT4 as a lysine deitaconylase that regulates macrophage inflammatory responses. Itaconate is a metabolite abundantly produced in activated macrophages. We find it forms a protein modification called lysine itaconylation. Using biochemical and proteomics approaches, we demonstrate that SIRT4 efficiently removes this modification from target proteins both in vitro and in vivo. In macrophages, SIRT4 expression increases upon LPS stimulation, coinciding with elevated protein itaconylation. SIRT4-deficient macrophages exhibit significantly increased IL-1β production in response to LPS stimulation. This phenotype is intrinsic to macrophages, as demonstrated by both SIRT4 knockdown and lentiviral over-expression models. Mechanistically, we identify key enzymes in branched-chain amino acid (BCAA) metabolism as targets of hyperitaconylation in SIRT4-deficient macrophages. The BCKDH complex component dihydrolipoamide branched chain transacylase E2 (DBT) is hyperitaconylated in SIRT4KO macrophages, concomitant with reduced BCKDH activity. Physiologically, SIRT4-deficient mice exhibit significantly delayed wound healing, demonstrating a consequence of dysregulated macrophage function. Our data reveal a novel protein modification pathway in immune cells and establish SIRT4 as a critical regulator at the intersection of metabolism and inflammation. These findings have implications for understanding immune dysregulation in aging and metabolic disease. |
| HostingRepository | jPOST |
| AnnounceDate | 2026-05-13 |
| AnnouncementXML | Submission_2026-05-12_08:00:04.424.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Paul Grimsrud |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
| ModificationList | S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-05-12 12:34:01 | ID requested | |
| ⏵ 1 | 2026-05-12 08:00:04 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Protein Itaconylation, SIRT4, Macrophage |
Contact List
| Matthew D. Hirschey | |
|---|---|
| lab head | |
| Paul Grimsrud | |
| contact affiliation | Duke University |
| dataset submitter | |
Full Dataset Link List
| jPOST dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST003806/ |
