PXD066631-1

PXD066631 is an original dataset announced via ProteomeXchange.

Title	Btg2 Inhibits the UFMylation of Fmo1 thus Restricting Taurine Synthesis and Exacerbating Ferroptosis in Hepatic Ischemia-Reperfusion Injury in Mice
Description	Hepatic ischemia‒reperfusion (I/R) injury (HIRI) represents a frequently occurring pathological phenomenon during liver surgery, yet the mechanisms governing HIRI remain inadequately comprehended. This study intends to explore the role of B-cell translocation gene 2 (Btg2) in HIRI. We find that Btg2 expression is up-regulated following HIRI. We subsequently develop an HIRl model utilizing hepatocyte-specific Btg2 transgenic over-expression and systemic Btg2 knockout male mice, discovering that Btg2 deletion mitigates inflammation and apoptosis. Furthermore, cellular experiments confirm that Btg2 knockdown alleviates inflammation and mitochondrial stress generated by hypoxia/reoxygenation (H/R). Metabolomics reveals enrichment of taurine metabolism pathway in the Btg2-/- mice. Mechanistically, we demonstrate that Btg2 restricts the UFMylation of flavin-containing monooxygenase 1 (Fmo1), the essential enzyme for taurine synthesis, by the E3 ligase UFM1-specific ligase 1 (Ufl1), consequently facilitating the K48 ubiquitination-mediated degradation of Fmo1. Adeno-associated virus-mediated Fmo1 over-expression inhibits ferroptosis and HIRI significantly in vivo, while adenovirus-mediated Btg2 over-expression mitigates ferroptosis and hypoxia/reoxygenation damage in vitro. Moreover, virtual screening of natural compounds reveals that Daturataturin A inhibits Btg2 and attenuates ferroptosis and HIRI sufficiently. These results propose that Btg2 may constitute a promising therapeutics target for HIRI.
HostingRepository	iProX
AnnounceDate	2025-07-25
AnnouncementXML	Submission_2025-07-27_20:29:45.890.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dadi Peng
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-27 20:29:28	ID requested
⏵ 1	2025-07-27 20:29:46	announced

Dataset with its publication pending

submitter keyword: HIRI, taurine, ferroptosis, inflammatory response

Zhongjun Wu
contact affiliation	Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University
contact email	wzjtcy@126.com
lab head
Dadi Peng
contact affiliation	Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University
contact email	dadi_peng@163.com
dataset submitter

iProX dataset URI