PXD047493-1

PXD047493 is an original dataset announced via ProteomeXchange.

Title	Hydrogen sulfide mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small-cell lung cancer
Description	Ferroptosis, a novel form of regulated cell death triggered by the iron-dependent peroxidation of phospholipids, offers promising penitential for cancer therapy. Hydrogen sulfide (H2S), an endogenous metabolite of the transsulfuration pathway, has been implicated in ferroptosis. However, the precise regulatory mechanisms remain elusive. In this study, we systematically investigated the role of exogenous hydrogen sulfide in ferroptosis regulation in non-small-cell lung cancer (NSCLC). We demonstrated that H2S sensitizes NSCLC to ferroptosis both in vitro and in vivo. Mechanistically, hydrogen sulfide persulfurates the 195th cysteine residue of S-adenosyl homocysteine hydrolase (SAHH), thus impeding the binding of SAHH to its substrate S-adenosyl homocysteine (SAH). Consequently, this inhibition reduces SAHH activity, leading to a decreased homocysteine level. This reduction in homocysteine subsequently results in diminished levels of cysteine and glutathione, particularly under conditions of cystine depletion, which collectively potentiate the occurrence of ferroptosis. Together, our findings unveil H2S as pivotal regulator for homocysteine metabolism, increasing the sensitivity of NSCLC to ferroptosis. Importantly, these findings highlight its potential therapeutic value for enhancing ferroptosis-based cancer therapies for NCSCLC.
HostingRepository	iProX
AnnounceDate	2023-12-04
AnnouncementXML	Submission_2023-12-21_22:48:38.470.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hualei Zheng
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro; QTRAP 5500

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-03 23:57:49	ID requested
⏵ 1	2023-12-21 22:48:38	announced

Dataset with its publication pending

submitter keyword: Ferroptosis,Transsulfuration pathway,Hydrogen sulfide (H2S),Persulfidation,S-adenosyl homocysteine hydrolase (SAHH)

Yongyou Zhang
contact affiliation	Xiamen University
contact email	yongyouzhang@xmu.edu.cn
lab head
Hualei Zheng
contact affiliation	Xiamen University
contact email	hlzheng12300@163.com
dataset submitter

iProX dataset URI