PXD043952 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Iron Drives Anabolic Metabolism Through Active Histone Demethylation and mTORC1 |
Description | All living cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here, we report a universal eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter and RAPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency (ID) supersedes other nutrient inputs into mTORC1. This process occurs in vivo, and is not an indirect effect by canonical iron-utilizing pathways. These data demonstrate a novel mechanism of eukaryotic iron sensing through dynamic chromatin remodeling and repression of mTORC1 mediated anabolism. Due to ancestral eukaryotes sharing homologues of KDMs and mTORC1 core components, this pathway likely predated the emergence of the other kingdom-specific nutrient sensors for mTORC1. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:54:23.931.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hsiang-Chun Chang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monomethylated residue; trimethylated residue; acetylated residue; dimethylated residue |
Instrument | TSQ Quantum Ultra |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-20 05:51:59 | ID requested | |
1 | 2023-07-20 06:46:43 | announced | |
⏵ 2 | 2024-10-22 05:54:24 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: histone, mTORC1,iron, methyation |
Contact List
Hossein Ardehali |
contact affiliation | Feinberg Cardiovascular Research Institute, Northwestern University |
contact email | h-ardehali@northwestern.edu |
lab head | |
Hsiang-Chun Chang |
contact affiliation | Northwestern University |
contact email | jimmy.h.chang.work@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043952
- Label: PRIDE project
- Name: Iron Drives Anabolic Metabolism Through Active Histone Demethylation and mTORC1