PXD058781

PXD058781 is an original dataset announced via ProteomeXchange.

Title	Modulatory Effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase Repair Function during Alcohol-Induced Hepatic Damage
Description	Alcohol-related liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg2+) deficiency, which can influence the liver disease progression. The mechanisms underlying Mg2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in ALD patients and preclinical animal models. In this study, CNNM4 is upregulated in the liver of both ALD patients and animal models. CNNM4 overexpression triggers Mg²⁺ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N-acetylgalactosamine (GalNAc) silencing RNA (siRNA) technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating ER stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases SAMe levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment. These findings shed light on the dysregulation of Mg2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. GalNAc siCnnm4 therapy boost the repair processes of ethanol damaged proteins through the upregulation of PCMT1 activity.
HostingRepository	PRIDE
AnnounceDate	2025-07-21
AnnouncementXML	Submission_2025-07-20_16:54:38.429.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
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	2024-12-11 09:40:34	ID requested
⏵ 1	2025-07-20 16:54:39	announced

10.1097/hep.0000000000001156;

Gonz, á, lez-Recio I, Goikoetxea-Usandizaga N, Rejano-Gordillo CM, Conter C, Rodr, í, guez Agudo R, Serrano-Maci, á M, Zapata-Pavas LE, Pe, ñ, a-Sanf, é, lix P, Azkargorta M, Elortza F, Herranz JM, Guillamon Thiery Á, Guerra-Ruiz AR, Jover R, Galicia-Garcia U, Mart, í, n C, Schaeper U, Delgado TC, D, í, az-Moreno I, D, í, az Quintana A, Buccella D, Nogueiras R, Argemi J, Á, vila MA, Gratac, ó, s-Gin, è, s J, Iruzubieta P, Pose E, Bataller R, Crespo J, Mart, í, nez-Cruz LA, Mart, í, nez-Chantar ML, Modulatory effects of CNNM4 on protein- l -isoaspartyl- O -methyltransferase repair function during alcohol-induced hepatic damage. Hepatology, 82(2):388-404(2025) [pubmed]

submitter keyword: ALD, Liver disease, Mg++,CNNM4

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE Bizkaia Tech. Park Build. 800 48160 Derio (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
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/2025/07/PXD058781

PRIDE project URI

• PRIDE
  1. PXD058781
     1. Label: PRIDE project
     2. Name: Modulatory Effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase Repair Function during Alcohol-Induced Hepatic Damage