PXD074828

PXD074828 is an original dataset announced via ProteomeXchange.

Title	Thioredoxin-interacting Protein Targets PRDX3 to Induce Mitochondria-associated Ferroptosis and Promote MASLD
Description	Hepatocyte ferroptosis has emerged as a pivotal driver of metabolic dysfunction-associated steatotic liver disease (MASLD), yet the mechanisms coupling metabolic stress to the ferroptotic machinery remain elusive. Here, we identify thioredoxin-interacting protein (TXNIP) as a requisite mediator of mitochondria-associated ferroptosis during MASLD progression. Interrogation of clinical datasets and experimental models revealed that hepatic TXNIP is robustly upregulated in MASH patients, positively correlated with disease severity and pro-ferroptotic gene signatures. Txnip-deficient mice conferred significant protection against high-fat diet-induced steatohepatitis and hepatic ferroptosis. Mechanistically, metabolic stress triggers the mitochondrial translocation of TXNIP, where it directly interacts with the mitochondrial-specific peroxidase Peroxiredoxin 3 (PRDX3). This physical association suppresses PRDX3 antioxidant activity, leading to mitochondrial reactive oxygen species (ROS) accumulation, iron overload, and lipid peroxidation. Functional rescue experiments confirmed that PRDX3 overexpression effectively abrogates TXNIP-induced ferroptosis, whereas PRDX3 silencing exacerbates the ferroptotic phenotype in TXNIP-overexpressing cells. Collectively, these findings establish the TXNIP-PRDX3 axis as a critical regulatory hub for mitochondrial redox homeostasis and identify this interaction as a potential therapeutic vulnerability to arrest MASLD progression.
HostingRepository	iProX
AnnounceDate	2026-02-15
AnnouncementXML	Submission_2026-02-26_22:44:37.707.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wentin Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-24 18:29:00	ID requested
⏵ 1	2026-02-26 22:44:38	announced

Dataset with its publication pending

submitter keyword: TXNIP, PRDX3, mitochondria-associated ferroptosis, MASLD

Wentin Zhang
contact affiliation	Shanxi Medical University
contact email	zhangwenting64@sxmu.edu.cn
lab head
Wentin Zhang
contact affiliation	Shanxi Medical University
contact email	zhangwenting64@sxmu.edu.cn
dataset submitter

iProX dataset URI