PXD063156

PXD063156 is an original dataset announced via ProteomeXchange.

Title	Arg1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction
Description	Ischemic/hypoxic injury significantly damages vascular function, detrimentally im-pact-ing patient outcomes. Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction. The mecha-nism of this process remains elusive. Using rat models of ischemia and hypoxic vas-cular smooth muscle cells (VSMCs), we combined transmission electron microscopy, super-resolution microscopy, and metabolic analysis to analyze the structure and function change of mitochondrial cristae. Multi-omics approaches revealed arginase 1 (Arg1) upregulation in ischemic VSMCs, confirmed by in vivo and in vitro knock-out models showing Arg1's protective effects on mitochondrial cristae, mitochondrial and vascular function, and limited the release of mtDNA. Mechanistically, Arg1 in-teracting with Mic10 led to mitochondrial cristae remodeling, together with hypox-ia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs. The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway. ChIP-qPCR results demonstrated that lactate-mediated Arg1 up-regulation was due to H3K18la upregulation. VSMCs targeted nano-material PLGA-PEI-siRNA@PM-α-SMA (NP-siArg1) significantly improved vascular dysfunction. This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury: a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria, leading to mitochondria cristae disorder and mtDNA release, culminating in VSMCs PANopto-sis. Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alle-viate ischemia/hypoxia-induced vascular impairments
HostingRepository	PRIDE
AnnounceDate	2025-06-02
AnnouncementXML	Submission_2025-06-01_16:08:49.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Han She
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-21 09:25:28	ID requested
⏵ 1	2025-06-01 16:08:49	announced

She H, Zheng J, Zhao G, Du Y, Tan L, Chen ZS, Wu Y, Li Y, Liu Y, Sun Y, Hu Y, Zuo D, Mao Q, Liu L, Li T, Arginase 1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction. Signal Transduct Target Ther, 10(1):167(2025) [pubmed]

10.1038/s41392-025-02255-2;

submitter keyword: mtDNA,Ischemic/hypoxic injury, Mitochondria, Vascular dysfunction, Arg1

Han She
contact affiliation	Army medical university
contact email	mazuishehan@163.com
lab head
Han She
contact affiliation	Army Medical University
contact email	mazuishehan@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD063156

PRIDE project URI

• PRIDE
  1. PXD063156
     1. Label: PRIDE project
     2. Name: Arg1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction