PXD055467

PXD055467 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics analysis of liver from LONP1 Knockout mice
Description	The mechanisms of hepatic stellate cell (HSC) activation and the development of liver fibrosis remains largely unknow. Here, we revealed a fibrosis related mechanism of hepatocytes-HSCs crosstalk regulated by hepatocyte LONP1. We demonstrate that hepatocyte LONP1 expression is decreased in HFD-fed mice and MASH patients. Liver-specific LONP1 deficiency increases orotic acid level and aggravates MASH-induced liver fibrosis in mice. We have identified DHODH as a substrate that is selectively degraded by LONP1 in an ATP-dependent manner. Moreover, activation of LONP1 reduces orotic acid levels and alleviates MASH-induced fibrosis in mice. Mechanistically, LONP1 mediates DHODH turnover, maintaining lower orotic acid levels to inhibit ATF3-mediated HSC proliferation and activation, thereby preventing liver fibrosis. Furthermore, plasma orotic acid levels are negatively correlated with liver LONP1 levels in humans. Therefore, targeting LONP1-mediated hepatocyte-HSC communication may represent a promising therapeutic strategy for MASH-induced liver fibrosis.
HostingRepository	PRIDE
AnnounceDate	2025-09-23
AnnouncementXML	Submission_2025-09-23_07:25:07.397.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dengqiu Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-02 02:38:47	ID requested
⏵ 1	2025-09-23 07:25:08	announced

10.1016/j.jhep.2025.07.013;

Xu D, Zhang Z, Zhu Z, Wei W, Bai Y, Wang W, Zhu Y, Alimujiang A, Shi Y, Zhang Z, Li Z, Wu P, Sun B, Decreased LONP1 expression exacerbates MASH-induced liver fibrosis via elevated orotic acid levels. J Hepatol, ():(2025) [pubmed]

submitter keyword: LONP1

hepatic stellate cell

liver fibrosis

orotic acid

Dengqiu Xu
contact affiliation	The First Affiliated Hospital of Anhui Medical University
contact email	xudengqiu@nju.edu.cn
lab head
Dengqiu Xu
contact affiliation	Anhui Medical University
contact email	xudengqiu@nju.edu.cn
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/2025/09/PXD055467

PRIDE project URI

• PRIDE
  1. PXD055467
     1. Label: PRIDE project
     2. Name: Quantitative proteomics analysis of liver from LONP1 Knockout mice