PXD043952-1

PXD043952 is an original dataset announced via ProteomeXchange.

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	2023-07-20
AnnouncementXML	Submission_2023-07-20_06:46:42.921.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hsiang-ChunChang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; trimethylated residue; acetylated residue; dimethylated residue
Instrument	TSQ Quantum Ultra

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.

Dataset with its publication pending

submitter keyword: histone, mTORC1,iron, methyation

HosseinArdehali
contact affiliation	Feinberg Cardiovascular Research Institute, Northwestern University
contact email	h-ardehali@northwestern.edu
lab head
Hsiang-ChunChang
contact affiliation	Northwestern University
contact email	jimmy.h.chang.work@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043952
     1. Label: PRIDE project
     2. Name: Iron Drives Anabolic Metabolism Through Active Histone Demethylation and mTORC1