PXD036682

PXD036682 is an original dataset announced via ProteomeXchange.

Title	Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damag
Description	Acetaminophen (APAP) is one of the most widely consumed and prescribed drugs. APAP overdose is one of the leading causes of intrinsic drug-induced liver injury (DILI), acute liver failure (ALF), and liver transplantation in the Western world. Mg2+, essential for health, plays a role in virtually every process within the human cell. The cellular transporter family cyclin M, also known as CNNM, plays a key role in Mg2+ transport across the cell membranes in different organs. Here, we identified that the expression of CNNM4 is elevated in the liver of patients with APAP-induced liver injury (AILI), with a concomitant disturbance in serum Mg2+ levels. We demonstrated that, in the liver, APAP interferes with the Mg2+ mitochondrial reservoir via CNNM4, which affects ATP production and ROS generation, further boosting endoplasmic reticulum (ER) stress of the hepatocytes. Importantly, the CNNM4 mutant T495I showed no effect. Finally, a shift in localization of CNNM4 from membrane to ER was shown under APAP toxicity. Therapeutic targeting of Cnnm4 in the liver with nanoparticles and GalNAc-formulated siRNA provides efficient protection from AILI by restoring hepatocyte Mg2+ homeostasis and by inducing hepatocyte restoration. Our results suggest that inhibition of Cnnm4 may represent an alternative route for the treatment of DILI..
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:43:05.246.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	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 08:48:00	ID requested
1	2023-03-11 06:31:21	announced
⏵ 2	2023-11-14 08:43:13	announced	2023-11-14: Updated project metadata.

Gonz, á, lez-Recio I, Sim, ó, n J, Goikoetxea-Usandizaga N, Serrano-Maci, á M, Mercado-G, ó, mez M, Rodr, í, guez-Agudo R, Lachiondo-Ortega S, Gil-Pitarch C, Fern, á, ndez-Rodr, í, guez C, Castellana D, Latasa MU, Abecia L, Anguita J, Delgado TC, Iruzubieta P, Crespo J, Hardy S, Petrov PD, Jover R, Avila MA, Mart, í, n C, Schaeper U, Tremblay ML, Dear JW, Masson S, McCain MV, Reeves HL, Andrade RJ, Lucena MI, Buccella D, Mart, í, nez-Cruz LA, Mart, í, nez-Chantar ML, Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage. Nat Commun, 13(1):6816(2022) [pubmed]

submitter keyword: Acetaminophen (APAP), CNNM4, drug-induced liver damage (DILI), acute liver failulre (ALF), label free

Felix ELortza
contact affiliation	Proteomics Service 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/2023/03/PXD036682

PRIDE project URI

• PRIDE
  1. PXD036682
     1. Label: PRIDE project
     2. Name: Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damag