PXD069433
PXD069433 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Macrophage MERTK restrains GRAMD1A‑driven mitochondrial cholesterol trafficking to limit colitis |
| Description | Failed clearance of apoptotic cells drives pathogen persistence, tissue damage, and damage associated molecular patterns accumulation, fueling immune remodeling. Despite its pathophysiological significance, the precise immunometabolic reprogramming underlying impaired phagocytic signaling in macrophages remains poorly defined. Here, we reveal a correlation between Crohn’s disease (CD) activity and MERTK⁺ macrophage abundance, establishing a previously unrecognized link between MERTK signaling and the orchestrated regulation of mitochondrial bioenergetics and cholesterol homeostasis. MERTK deficiency activates cholesterol biosynthesis in the endoplasmic reticulum (ER) and disrupts the protein degradation of the cholesterol transporter GRAM Domain Containing 1A (GRAMD1A) localized to the ER. Combined live-cell imaging and metabolomics show enhanced ER-to-mitochondria cholesterol trafficking, oxysterol accumulation, and impaired oxidative phosphorylation. Critically, this mitochondrial dysfunction activates innate immune signaling cascades by releasing mtDNA and dsRNA. Our findings define an elegant mechanistic axis linking defective efferocytosis to metabolic reprogramming and inflammatory disease pathogenesis. |
| HostingRepository | iProX |
| AnnounceDate | 2025-10-14 |
| AnnouncementXML | Submission_2025-10-14_01:21:02.260.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Juanhan Liu |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | (13)C labeled residue |
| Instrument | timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-10-14 01:20:48 | ID requested | |
| ⏵ 1 | 2025-10-14 01:21:02 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Crohn's Disease, MerTK, Macrophage, Inflammation |
Contact List
| Jianan Ren | |
|---|---|
| contact affiliation | Nanjing University |
| contact email | Jiananr@gmail.com |
| lab head | |
| Juanhan Liu | |
| contact affiliation | Nanjing University |
| contact email | 1558940856@qq.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
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